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The aim of this study was to evaluate the combined effects of L-arginine, intermittent hypoxia training (IHT), and acute stress on oxygen-dependent processes in rats, including mitochondrial oxidative phosphorylation, microsomal oxidation, and the intensity of lipoperoxidation processes. In addition, our study investigated how the modulatory effect of the NO synthase mechanism on the concentration of catecholamines (CA), such as adrenaline and noradrenaline, and their biosynthetic precursors (DOPA, dopamine) varies depending on the cholinergic (acetylcholine, Ach-acetylcholinesterase, AChE) status in rats. This study investigated the protective stress-limiting effects of L-arginine impact and IHT in the blood and liver of rats. The results showed that L-arginine promoted the maintenance of NAD-dependent oxidation in mitochondria, which was detrimental compared to succinate oxidation, and was accompanied by depletion of respiratory activity reserves under stress induced by high concentrations of CA. The interdependence of SC-dependent oxidation and the functional role of NAD-dependent substrate oxidation in the mitochondrial respiratory chain in stress conditions induced using inhibitors revealed the importance of the NO system. Administration of L-arginine during the IHT course prior to stress exposure increased the compensatory capacity of the organism. L-arginine increased the compensatory capacity of the sympathoadrenal system in stress-exposed rats. In the early stages of IHT, modulation of the CA concentration was observed with a concomitant increase in lipoperoxidation processes, and in the final stages of IHT, the CA concentrations increased, but there was also an inhibition of lipoperoxidation, which was particularly enhanced by the administration of L-arginine. The increase in blood concentrations of CA and ACh was accompanied by a decrease in AChE activity at different stages of adaptation to hypoxia induced by IHT (days 5, 10, and 14). Thus, the IHT method significantly mobilises the reserve capacity of oxygen-dependent processes through the system of CA, ACh-AChE mediated by nitric oxide.

Knowledge about determinants of addiction in people taking addictive substances is poor and needs to be supplemented. The novelty of this paper consists in the analysis of innovative aspects of current research about relationships between determinants of addiction in Polish patients taking addictive substances and rare available data regarding the relationships between these factors from studies from recent years from other environments, mainly in Europe, and on the development of genetic determinants of physiological responses. We try to explain the role of the microelements Mn, Fe, Cu, Co, Zn, Cr, Ni, Tl, Se, Al, B, Mo, V, Sn, Sb, Ag, Sr, and Ba, the toxic metals Cd, Hg, As, and Pb, and the rare earth elements Sc, La, Ce, Pr, Eu, Gd, and Nd as factors that may shape the development of addiction to addictive substances or drugs. The interactions between factors (gene polymorphism, especially ANKK1 ( TaqI A ), ANKK1 ( Taq1 A-CT ), DRD2 ( TaqI B , DRD2 Taq1 B-GA , DRD2 Taq1 B-AA , DRD2-141C Ins/Del ), and OPRM1 ( A118G )) in patients addicted to addictive substances and consumption of vegetables, consumption of dairy products, exposure to harmful factors, and their relationships with physiological responses, which confirm the importance of internal factors as determinants of addiction, are analyzed, taking into account gender and region. The innovation of this review is to show that the homozygous TT mutant of the ANKK1 TaqI A polymorphism rs 1800497 may be a factor in increased risk of opioid dependence. We identify a variation in the functioning of the immune system in addicted patients from different environments as a result of the interaction of polymorphisms.

Background/aims: Lead exposure is known to induce oxidative stress and neurotoxicity. Nitric oxide (NO) plays an important role in modulating oxidative stress, with L-arginine as a precursor of NO and N ω -nitro-L-arginine (L-NNA) as an inhibitor of NO synthase, an enzyme that catalyses the production of nitric oxide (NO) from L-arginine., Methods: This study investigated the differential effects of L-arginine and L-NNA on markers of oxidative stress and biochemical changes in brain tissue from rats with different levels of resistance to hypoxia exposed to lead nitrate. Rats with either low or high resistance to hypoxia were exposed to lead nitrate (oral 3.6 mg lead nitrate/kg b.w. per day for 30 days) and treated with L-arginine (600 mg/kg b.w., i.p., 30 min before and after exposure to lead nitrate) or L-NNA (35 mg/kg b.w., i.p., 30 min before and after exposure to lead nitrate). Brain tissue samples were analysed for lipid peroxidation, oxidative modification of proteins, and activity of antioxidant enzymes, including superoxide dismutase, catalase, glutathione reductase, and peroxidase, and total antioxidant status (TAS). We also examined the biomarkers of biochemical pathways involving the activity of alanine and aspartate aminotransferases, succinate dehydrogenase (SDH), and α-ketoglutarate dehydrogenase (KGDH). In addition, the trend observed was supported by assessments of the acetylcholine levels and acetylcholinesterase activity (ACh-AChE system) in brain tissue., Results: In rats with low resistance to hypoxia, the L-arginine treatment significantly reduced lipid peroxidation and oxidative protein modification but increased antioxidant enzyme activity, suggesting a protective effect against lead-induced oxidative stress. Conversely, in rats with high resistance to hypoxia, L-NNA had a protective effect, reducing lead-induced oxidative damage and decreasing lipid peroxidation, whereas L-arginine exacerbated oxidative stress and impaired antioxidant defences. These findings were supported by corresponding changes in the acetylcholine-acetylcholinesterase system, reflecting the observed patterns of lead-induced oxidative stress and neurotoxicity. The study shows that L-arginine exerts a protective effect by reducing lead-induced oxidative damage via an improvement in TAS. Our study shows that lead nitrate exposure significantly increases ala-nine and aspartate aminotransferase activity in brain tissue, with L-arginine exacerbating and L-NNA reversing this effect. The lead nitrate exposure also affected the activities of SDH and KGDH, which are important for cellular energy production and hypoxia resistance, with L-arginine altering SDH activity depending on the level of resistance and L-NNA enhancing both SDH and KGDH activities. These trends were further validated by alterations in the ACh-AChE system, highlighting the differential role of NO-dependent mechanisms in modulating lead-induced neurotoxicity based on hypoxia resistance., Conclusion: These findings suggest potential targeted therapeutic strategies based on the oxidative stress profile and highlight the potential of nitric oxide system modulators in counteracting lead-induced biochemical alterations and the dynamics of the ACh-AChE system depending on the individual physiological reactivity of organisms., Competing Interests: The authors have no competing interests to declare., (© Copyright by the Author(s). Published by Cell Physiol Biochem Press.)

Male infertility is a world multifactorial problem modulated by environmental and genetic factors. Male aspects account for 20-50 % of infertility cases. Our results are unique because they treat the importance of components participating in the determination of male infertility (environmental and immunogenetic determinants, seminological analysis, lipoperoxidation, genetic determinants, role of aluminum, arsenic, cadmium and boron). We analyzed agents affecting male reproductive potential (aluminum, boron, cadmium, arsenic, lipid peroxidation, gene polymorphisms (MTHFRv.C677T (rs1801133) (chromosome-1) and IL-4v.C589T (rs2243250) (chromosome-5) in men with semen disorders (n=76) and with normozoospermia (n=87) from Central Poland. Polymorphisms of MTHFRv.C677T and IL-4v.C589T genes indirectly shape toxic metals concentration and lipoperoxidation but do not exert direct influence on male fertility disorders (monomorphism and lack of differences in genotypes frequency). Men with genotype TT or CC (IL-4v.C589T) show some differentiation in elements concentration and intensity of lipoperoxidation. Analysis of TT or CC (IL-4v.C589T) genotype brought correlations with B, Al, Cd, and lipoperoxidation (P<0.05) and suggesting that mentioned factors jointly shape male reproductive capability. Toxic metals may play an important role in shaping of men genetic polymorphisms, since Cd was identified as a factor increasing risk of qualification to infertile group, predisposing to fertility disorders. B, Al and Cd may be considered as important modulators of reproductive condition. However, lipoperoxidation as an isolated predictive parameter does not produce convincing results in male reproductive potential (higher MDA concentration in healthy men). Our results may be helpful in the diagnosis of male infertility, in the reduction of idiopathic cases of unknown origin and in implementation of targeted and more effective treatment (pharmacological, hormonal). Identification of environmental stressors and their correlations with fertility disorders can help to eliminate or reduce the impact of factors unfavorable to fertility. Our results highlight the importance of environmental and immunogenetic factors in shaping of defensive potential against destruction of spermatozoa and infer a role of oxidative stress in the induction of gene polymorphisms, affecting male fertility., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: This study aimed to evaluate biomarkers of oxidative stress (2-thiobarbituric acid reactive substances, aldehyde and ketone derivatives of oxidatively modified proteins and total antioxidant capacity), the activity of antioxidant enzymes (superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase), that of lysosomal enzymes (alanyl aminopeptidase, leucyl aminopeptidase, β-N-acetylglucosaminidase and acid phosphatase) and changes in biochemical parameters (alanine aminotransferase, aspartate aminotransferase, de Ritis ratio, lactate dehydrogenase activity, lactate and pyruvate levels and their ratio) in the liver tissue of fish that were vaccinated against enteric redmouth disease and challenged with its causative agent, the bacterium Yersinia ruckeri ., Material and Methods: The vaccine was administered orally to trout, some of which were challenged with Y. ruckeri 61 days later. For comparison, unvaccinated and unchallenged trout and unvaccinated and challenged trout were also evaluated., Results: In the unvaccinated fish, infection with Y. ruckeri disrupted the pro-oxidant/antioxidant balance, led to a significant increase in lipid peroxidation and oxidative modification of proteins, decreased total antioxidant capacity and significantly increased the activity of lysosomal enzymes. In vaccinated fish, the Y. ruckeri challenge increased the activity of glutathione-related enzymes and decreased lipid peroxidation, anaerobic metabolism and the activity of lysosomal enzymes in fish livers relative to the unvaccinated and challenged group. In contrast, these parameters increased after the Y. ruckeri challenge in unvaccinated trout relative to those in the untreated group., Conclusion: Vaccination exerted a protective effect during the Y. ruckeri challenge and had no adverse effect on fish livers., Competing Interests: Conflict of Interests Statement: The authors declare that there is no conflict of interests regarding the publication of this article., (© 2024 Natalia Kurhaluk et al., published by Sciendo.)

Background/aims: Assessment of the levels of vital blood parameters in donors is essential to evaluate their health status, ensure their suitability for donation, preserve the integrity of the circulatory system, and facilitate comprehensive health monitoring. The aim of our study was to analyse the levels of haemoglobin, haematocrit, erythrocyte count, MCV, MCH, and MCHC in 12 groups of first-time donors and experienced donors of both sexes at the John Paul II Regional Blood Donation and Treatment Centre in Słupsk, northern Poland. The donors were divided into three age groups (18-30 years, 31-45 years, and 46-65 years)., Methods: Using MANOVA multivariate significance tests, we examined the main effects of donor-related factors (age, sex, donor stage) on morphological blood parameters to evaluate different haematological parameters, such as Hb, Ht, RBC, MCV, MCH, and MCHC, and identified statistically significant relationships between all variables., Results: The multivariate analysis of these three main factors showed that the variation in haemoglobin (Hb) levels accounted for 46% of the explained dependence in this statistical model. In particular, approximately half of the variability in the multivariate statistical analysis was attributed to the role of Hb and haematocrit (Ht). In addition, the β-coefficient values for Hb and Ht were statistically higher in relation to donor sex and donor type (single versus repeat). These β-coefficient values from our data represent the strength and direction of the relationship between the haematological parameters (Hb and Ht) and the specific donor characteristics. A higher β-coefficient indicates a stronger influence of donor sex and donor type on these parameters, suggesting that these factors contribute significantly to the variation in the Hb and Ht levels. Based on our results, the comprehensive analysis of the entire statistical model of metabolic biomarkers revealed the following hierarchy: Hb > Ht > MCHC > MCV > RBC > MCH. The results obtained showed strong statistical relationships, as indicated by the high values of the key statistical indicators in our analysis. The coefficient of determination (R²) showed that the model explained a significant proportion of the variance in the data, while the F-test statistic confirmed the significance of the predictors., Conclusion: These strong statistical dependencies provided a clear justification for selecting this model over others, as it effectively represented the underlying relationships within the data. These statistics help to assess how well the model matches the actual data, thereby helping to reduce the risks associated with blood donation, optimise donor safety, and maintain the quality and efficiency of blood transfusion services., Competing Interests: The authors have no competing interests to declare., (© Copyright by the Author(s). Published by Cell Physiol Biochem Press.)

Stroke is the second leading cause of death worldwide, and its incidence is rising rapidly. Acute ischemic stroke is a subtype of stroke that accounts for the majority of stroke cases and has a high mortality rate. An effective treatment for stroke is to minimize damage to the brain's neural tissue by restoring blood flow to decreased perfusion areas of the brain. Many reports have concluded that both oxidative stress and excitotoxicity are the main pathological processes associated with ischemic stroke. Current measures to protect the brain against serious damage caused by stroke are insufficient. For this reason, it is important to investigate oxidative and antioxidant strategies to reduce oxidative damage. This review focuses on studies assessing the concentration of oxidative stress biomarkers and the level of antioxidants (enzymatic and non-enzymatic) and their impact on the clinical prognosis of patients after stroke. Mechanisms related to the production of ROS/RNS and the role of oxidative stress in the pathogenesis of ischemic stroke are presented, as well as new therapeutic strategies aimed at reducing the effects of ischemia and reperfusion.

Ageing is a natural ontogenetic phenomenon that entails a decrease in the adaptive capacity of the organism, as a result of which the body becomes less adaptable to stressful conditions. Nitrate and nitrite enter the body from exogenous sources and from nitrification of ammonia nitrogen by intestinal microorganisms. This review considers the mechanisms of action of l-arginine, a known inducer of nitric oxide (NO) biosynthesis, and nitrates as supplements in the processes of ageing and aggravated stress states, in which mechanisms of individual physiological reactivity play an important role. This approach can be used as an element of individual therapy or prevention of premature ageing processes depending on the different levels of initial reactivity of the functional systems. A search was performed of the PubMed, Scopus, and Google Scholar databases (n = 181 articles) and the author's own research (n = 4) up to May 5, 2023. The review presents analyses of data on targeted treatment of NO generation by supplementation with l-arginine or nitrates, which is a promising means for prevention of hypoxic conditions frequently accompanying pathological processes in an ageing organism. The review clarifies the role of the individual state of physiological reactivity, using the example of individuals with a high predominance of cholinergic regulatory mechanisms who already have a significant reserve of adaptive capacity. In studies of the predominance of adrenergic influences, a poorly trained organism as well as an elderly organism correspond to low resistance, which is an additional factor of damage at increased energy expenditure., Conclusion: It is suggested that the role of NO synthesis from supplementation of dietary nitrates and nitrites increases with age rather than from oxygen-dependent biosynthetic reactions from l-arginine supplementation., (© The Author(s) 2023. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background/aims: Individual resistance to hypoxia is an important feature of the physiological profile of an organism, particularly in relation to lead-induced toxicity., Methods: Our study focused on evaluating parameters of mitochondrial oxygen consumption, microsomal oxidation, intensity of lipoperoxidation processes and antioxidant defences in the liver of rats with low (LR) and high (HR) resistance to hypoxia to elucidate the mechanisms of action of L-arginine and the NO synthase inhibitor L-NNA before or after exposure to lead nitrate., Results: Our study suggests that the redistribution of oxygen-dependent processes towards mitochondrial processes under the influence of the nitric oxide precursor amino acid L-arginine is an important mechanism for maintaining mitochondrial respiratory chain function during per os lead nitrate exposure (3.6 mg lead nitrate/kg bw per day for 30 days). Animals were given L-arginine at a dose of 600 mg/kg bw (i.p., 30 min) before and after exposure to lead nitrate or the NO synthase inhibitor N ω -nitro-L-arginine (L-NNA) at a dose of 35 mg/kg bw (i.p., 30 min) before and after exposure to lead nitrate. Our experiments demonstrated the efficacy of using lead nitrate to simulate lead-related toxic processes via Pb levels in liver tissue; we demonstrated significantly reduced levels of nitrites and nitrates, i.e. stable metabolites of the nitric oxide system, in both LR and HR animals. The effect of the amino acid L-arginine stabilised the negative effects of lead nitrate exposure in both groups of LR and HR rats. We observed the efficiency of mitochondrial energy supply processes and showed a greater vulnerability of NADH-dependent oxidation during lead nitrate exposure in the liver of HR rats., Conclusion: L-arginine initiated the processes of oxidation of NADH-dependent substrates in the LR group, whereas in the HR group this directionality of processes was more effective when the role of the nitric oxide system was reduced (use of L-NNA). Our study of key antioxidant enzyme activities in rat liver tissue during lead nitrate exposure revealed changes in the catalase-peroxidase activity ratio. We found different activities of antioxidant enzymes in the liver tissue of rats treated with lead nitrate and L-arginine or L-NNA, with a significant increase in GPx activity in the LR group when L-arginine was administered both before and after exposure to lead nitrate., Competing Interests: The authors have no competing interests to declare., (© Copyright by the Author(s). Published by Cell Physiol Biochem Press.)

Exposure to heavy metals and lifestyle factors like smoking contribute to the production of free oxygen radicals. This fact, combined with a lowered total antioxidant status, can induce even more damage in the development of ankylosing spondylitis (AS). Despite the fact that some researchers are looking for more genetic factors underlying AS, most studies focus on polymorphisms within the genes encoding the human leukocyte antigen (HLA) system. The biggest challenge is finding the effective treatment of the disease. Genetic factors and the influence of oxidative stress, mineral metabolism disorders, microbiota, and tobacco smoking seem to be of great importance for the development of AS. The data contained in this review constitute valuable information and encourage the initiation and development of research in this area, showing connections between inflammatory disorders leading to the pathogenesis of AS and selected environmental and genetic factors.

Age-related macular degeneration (AMD) is a chronic disease, which often develops in older people, but this is not the rule. AMD pathogenesis changes include the anatomical and functional complex. As a result of damage, it occurs, in the retina and macula, among other areas. These changes may lead to partial or total loss of vision. This disease can occur in two clinical forms, i.e., dry (progression is slowly and gradually) and exudative (wet, progression is acute and severe), which usually started as dry form. A coexistence of both forms is possible. AMD etiology is not fully understood. Extensive genetic studies have shown that this disease is multifactorial and that genetic determinants, along with environmental and metabolic-functional factors, are important risk factors. This article reviews the impact of heavy metals, macro- and microelements, and genetic factors on the development of AMD. We present the current state of knowledge about the influence of environmental factors and genetic determinants on the progression of AMD in the confrontation with our own research conducted on the Polish population from Kuyavian-Pomeranian and Lubusz Regions. Our research is concentrated on showing how polluted environments of large agglomerations affects the development of AMD. In addition to confirming heavy metal accumulation, the growth of risk of acute phase factors and polymorphism in the genetic material in AMD development, it will also help in the detection of new markers of this disease. This will lead to a better understanding of the etiology of AMD and will help to establish prevention and early treatment.

Background/aims: Important benefits of intermittent hypoxic training (IHT) have emerged as an effective tool for enhancing adaptive potential in different pathological states, among which acute hypoxia dominates. Therefore, the aim of our study was to evaluate the mechanisms related to the effects of the nitric oxide system (nitrites, nitrates, carbamide, and total polyamine content) on ADP-stimulated oxygen consumption and oxidative phosphorylation in heart and liver mitochondria and biomarkers of oxidative stress in the blood, heart, and liver of rats exposed to the IHT method and acute hypoxia and treated with the amino acid L-arginine (600 mg/kg, 30 min) or the NO synthase inhibitor L-NNA (35 mg/kg, 30 min) prior to each IHT session., Methods: We analysed the modulation of the system of oxygen-dependent processes (mitochondrial respiration with the oxygraphic method, microsomal oxidation, and lipoperoxidation processes using biochemical methods) in tissues during IHT in the formation of short-term and long-term effects (30, 60, and 180 days after the last IHT session) with simultaneous administration of L-arginine. In particular, we investigated how mitochondrial functions are modulated during intermittent hypoxia with the use of oxidation substrates (succinate or α-ketoglutarate) in bioenergetic mechanisms of cellular stability and adaptation., Results: The IHT method is associated with a significant increase in the production of endogenous nitric oxide measured by the levels of its stable metabolite, nitrite anion, in both plasma (almost 7-fold) and erythrocytes (more than 7-fold) of rats. The intensification of nitric oxide-dependent pathways of metabolic transformations in the energy supply processes in the heart and liver, accompanied by oscillatory mechanisms of adaptation in the interval mode, causes a probable decrease in the production of urea and polyamines in plasma and liver, but not in erythrocytes. The administration of L-arginine prior to the IHT sessions increased the level of the nitrite-reducing component of the nitric oxide cycle, which persisted for up to 180 days of the experiment., Conclusion: Thus, the efficacy of IHT and its nitrite-dependent component shown in this study is associated with the formation of long-term adaptive responses by preventing the intensification of lipoperoxidation processes in tissues due to pronounced changes in the main enzymes of antioxidant defence and stabilisation of erythrocyte membranes, which has a pronounced protective effect on the system of regulation of oxygen-dependent processes as a whole., Competing Interests: The authors have no competing interests to declare., (© Copyright by the Author(s). Published by Cell Physiol Biochem Press.)

There is still a need to investigate the relationships between glycophytes and halophytes and the many biotic and abiotic factors in their natural environments. Therefore, we study the effects of the type of environment on the ecophysiological responses and condition of the glycophyte Elder Sambucus nigra L., the macrophyte Common Reed Phragmites australis (Cav.) Trin. ex Steud., the facultative halophyte Weeping Alkaligrass Puccinellia distans (Jacq.) Parl, and the obligate halophyte Common Glasswort Salicornia europaea L. in a saline-disturbed anthropogenic region of central Poland. We analyzed the effects of salinity, acidity, and soil organic matter on shoot length, lipoperoxidation, and proline in roots and green parts, and evaluated plant responses to environmental disturbance, which allowed for the comparison of adaptation strategies. The studies were carried out in (1) "sodium production" (near sodium factories), (2) "anthropogenic environments" (waste dumps, agroecosystems, calcium deposits, post-production tanks), (3) "wetland environments" (near river channels and riparian areas), and (4) "control" (natural, unpolluted environments). Green parts of plants are better suited to indicate environmental stress than roots. Their higher structural MDA membrane damage is related to the transport of toxic ions to the shoots by a rapid transpiration stream in the xylem. We found high salinity to be the main factor inducing growth and found it to be correlated with the high pH effect on proline increase in glycophytes (Elder, Reed) and Weeping Alkaligrass, in contrast to Common Glasswort. We suggest that proline accumulation allows osmotic adjustment in the green parts of reeds and alkaligrasses, but may have another function (in Elder). Common Glasswort accumulates large amounts of Na + , which is energetically more effective than proline accumulation for osmotic adjustment. Organic matter affects plant growth and proline levels, but soil salinity and pH alter nutrient availability. Plant distribution along the salinity gradient indicates that Elder is the most salt-sensitive species compared to Reed, Alkaligrass, and Glasswort. Salinity and the lack of control of thick reeds, which compete with other plant groups, affect the distribution of halophytes in saline environments.

Relationships between protective enzymatic and non-enzymatic pro-antioxidant mechanisms and addictive substances use disorders (SUDs) are analyzed here, based on the results of previous research, as well as on the basis of our current own studies. This review introduces new aspects of comparative analysis of associations of pro-antixidant and neurobiological effects in patients taking psychoactive substances and complements very limited knowledge about relationships with SUDs from different regions, mainly Europe. In view of the few studies on relations between antioxidants and neurobiological processes acting in patients taking psychoactive substances, this review is important from the point of view of showing the state of knowledge, directions of diagnosis and treatment, and further research needed explanation. We found significant correlations between chemical elements, pro-antioxidative mechanisms, and lipoperoxidation in the development of disorders associated with use of addictive substances, therefore elements that show most relations (Pr, Na, Mn, Y, Sc, La, Cr, Al, Ca, Sb, Cd, Pb, As, Hg, Ni) may be significant factors shaping SUDs. The action of pro-antioxidant defense and lipid peroxidation depends on the pro-antioxidative activity of ions. We explain the strongest correlations between Mg and Sb, and lipoperoxidation in addicts, which proves their stimulating effect on lipoperoxidation and on the induction of oxidative stress. We discussed which mechanisms and neurobiological processes change susceptibility to SUDs. The innovation of this review is to show that addicted people have lower activity of dismutases and peroxidases than healthy ones, which indicates disorders of antioxidant system and depletion of enzymes after long-term tolerance of stressors. We explain higher level of catalases, reductases, ceruloplasmin, bilirubin, retinol, α-tocopherol and uric acid of addicts. In view of poorly understood factors affecting addiction, analysis of interactions allows for more effective understanding of pathogenetic mechanisms leading to formation of addiction and development the initiation of directed, more effective treatment (pharmacological, hormonal) and may be helpful in the diagnosis of psychoactive changes., Competing Interests: Declaration of Competing Interest The authors declare that have both no personal and financial conflict of interest to disclose (the authors declare no conflicts of any interest). All authors of this manuscript have read the manuscript and have agreed to submit it in its current form for consideration for publication., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Nutritional status disorders have the most significant impact on the development of cardiovascular and oncologic diseases; therefore, the interest in the study of palm oil as among the leading components of nutrition has been increasing. The data examined in this review were sourced from the Scopus, SCIE (Web of Science), PubMed and PubMed Central, MEDLINE, CAPlus/SciFinder, and Embase databases; experts in the field; bibliographies; and abstracts from review analyses from the past 15 years. This review summarizes recent research data focusing on the quantitative and qualitative composition of nutrition of modern humans; concepts of the relationship between high-fat diets and disorders of insulin functioning and transport and metabolism of fatty acids; analyses of data regarding the palmitic acid (16:0) to oleic acid (18:1) ratio; and the effect of diet based on palm oil consumption on cardiovascular risk factors and lipid and lipoprotein levels. Several studies suggest a potential vector contributing to the transmission of maternal, high-fat-diet-induced, addictive-like behaviors and obesogenic phenotypes across generations. The relationship between cholesterol accumulation in lysosomes that may lead to lysosome dysfunction and inhibition of the autophagy process is analyzed, as is the progression of inflammatory diseases, atherosclerosis, nonalcoholic liver inflammation, and obesity with associated complications. Data are discussed from analyses of differences between rodent models and human population studies in the investigated different effects of palm oil consumption as a high-fat diet component. A conclusion is reached that the results cannot be generalized in human population studies because no similar effects were observed. Although there are numerous published reports, more studies are necessary to elucidate the complex regulatory mechanisms in digestive and nutrition processes, because there are great differences in lipoprotein profiles between rodents and humans, which makes it difficult to reproduce the pathology of many diseases caused by different types of the high-fat diet., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Age-related macular degeneration (AMD) is a chronic disease that usually develops in older people. Pathogenetic changes in this disease include anatomical and functional complexes. Harmful factors damage the retina and macula. These changes may lead to partial or total loss of vision. The disease can occur in two clinical forms: dry (the progression is slow and gentle) and exudative (wet-progression is acute and severe), which usually starts in the dry form; however, the coexistence of both forms is possible. The etiology of AMD is not fully understood, and the precise mechanisms of the development of this illness are still unknown. Extensive genetic studies have shown that AMD is a multi-factorial disease and that genetic determinants, along with external and internal environmental and metabolic-functional factors, are important risk factors. This article reviews the role of glutathione (GSH) enzymes engaged in maintaining the reduced form and polymorphism in glutathione S-transferase theta-1 ( GSTT1 ) and glutathione S-transferase mu-1 ( GSTM1 ) in the development of AMD. We only chose papers that confirmed the influence of the parameters on the development of AMD. Because GSH is the most important antioxidant in the eye, it is important to know the influence of the enzymes and genetic background to ensure an optimal level of glutathione concentration. Numerous studies have been conducted on how the glutathione system works till today. This paper presents the current state of knowledge about the changes in GSH, GST, GR, and GPx in AMD. GST studies clearly show increased activity in ill people, but for GPx, the results relating to activity are not so clear. Depending on the research, the results also suggest higher and lower GPx activity in patients with AMD. The analysis of polymorphisms in GST genes confirmed that mutations lead to weaker antioxidant barriers and may contribute to the development of AMD; unfortunately, a meta-analysis and some research did not confirm that connection. Unspecific results of many of the parameters that make up the glutathione system show many unknowns. It is so important to conduct further research to understand the exact mechanism of defense functions of glutathione against oxidative stress in the human eye.

Introduction: Determination of morphological and biochemical blood indices facilitates assessment of the health and welfare of horses, their nutrient demand, the effects of training already undertaken, and the horses' suitability for exercise. Identification of the season-dependent components and the effects of sex and exercise on changes in frequently referenced haematological and biochemical parameters was the main goal of the current study., Material and Methods: The blood morphology of 21 healthy adult Shetland ponies (11 mares and 10 stallions) aged 6.5 ± 1.4 years from the central Pomeranian region in Poland was analysed. Blood samples were taken once per season for one year., Results: No statistically significant season-dependent differences were found in the blood morphology parameters in either mares or stallions before or after exercise. Beta-coefficient results revealed the strength and type of the relationship of red blood cell distribution width (RDW) and granulocyte count (GRA) with the season, of red blood cell count (RBC), haematocrit, mean corpuscular volume and mean platelet volume with the sex, and of RDW, white blood cell count, GRA and RBC with the exercise factor. Biomarkers demonstrating the relationship between aerobic and anaerobic levels of energy metabolism in the blood did not show any sex dependency in regression analysis., Conclusion: The sex-independence of energy metabolism biomarkers may indicate the universality of these parameters. Both seasonality itself and its combination with the exercise factor took part in the formation of effective adaptive reactions for maintenance of morphological blood indices in the ponies during exercise., Competing Interests: Conflict of Interests Statement: The authors declare that there is no conflict of interests regarding the publication of this article., (© 2024 Halina Tkaczenko et al., published by Sciendo.)

Environmental studies in Northern Poland are example of the functioning of ecophysiological relationships under anthropogenic impact. The aim of our studies was to investigate sex-dependent effects on the alterations in the concentration of chemical elements in soil samples collected from habitats of feral pigeon Columba livia f. urbana from Northern Poland, as well as feathers, biomarkers of oxidative stress, antioxidant defense, and total cholinesterase activity in tissues (liver, kidney, brain). Concentration of Si, Zn, and Pb in feathers of pigeons was significant. The levels of Si and Zn were higher in feathers of females from non-polluted, while higher Pb levels were found only in females from polluted areas (p = 0.000). This was confirmed by MANOVA of biomarkers of antioxidant defense, elements concentration, and revealing the order of effects: tissue type > environment > sex. Erythrocytes of males living in polluted areas were more fragile to hemolytic agents resulting in a higher percentage of hemolyzed erythrocytes. The effects of polluted environment on the level of carbonyl derivatives of oxidatively modified proteins compared to the effects of sex were more pronounced in the case of kidney (p = 0.000) and hepatic tissues (p = 0.000). Polluted areas were associated with significant increase in SOD activity in the brain and hepatic tissues of pigeons (p = 0.000). Health status of feral pigeons is significantly different in conditions of environmental destabilization., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Anti-ageing biology and medicine programmes are a focus of genetics, molecular biology, immunology, endocrinology, nutrition, and therapy. This paper discusses metabolic therapies aimed at prolonging longevity and/or health. Individual components of these effects are postulated to be related to the energy supply by tricarboxylic acid (TCA) cycle intermediates and free radical production processes. This article presents several theories of ageing and clinical descriptions of the top markers of ageing, which define ageing in different categories; additionally, their interactions with age-related changes and diseases related to α-ketoglutarate (AKG) and succinate SC formation and metabolism in pathological states are explained. This review describes convincingly the differences in the mitochondrial characteristics of energy metabolism in animals, with different levels (high and low) of physiological reactivity of functional systems related to the state of different regulatory systems providing oxygen-dependent processes. Much attention is given to the crucial role of AKG and SC in the energy metabolism in cells related to amino acid synthesis, epigenetic regulation, cell stemness, and differentiation, as well as metabolism associated with the development of pathological conditions and, in particular, cancer cells. Another goal was to address the issue of ageing in terms of individual characteristics related to physiological reactivity. This review also demonstrated the role of the Krebs cycle as a key component of cellular energy and ageing, which is closely associated with the development of various age-related pathologies, such as cancer, type 2 diabetes, and cardiovascular or neurodegenerative diseases where the mTOR pathway plays a key role. This article provides postulates of postischaemic phenomena in an ageing organism and demonstrates the dependence of accelerated ageing and age-related pathology on the levels of AKG and SC in studies on different species (roundworm Caenorhabditis elegans , Drosophila , mice, and humans used as models). The findings suggest that this approach may also be useful to show that Krebs cycle metabolites may be involved in age-related abnormalities of the mitochondrial metabolism and may thus induce epigenetic reprogramming that contributes to the senile phenotype and degenerative diseases. The metabolism of these compounds is particularly important when considering ageing mechanisms connected with different levels of initial physiological reactivity and able to initiate individual programmed ageing, depending on the intensity of oxygen consumption, metabolic peculiarities, and behavioural reactions.

Background/aims: Currently, it is proven that the cellular metabolism of nitric oxide is necessary to maintain optimal health and adaptation of the organism to the impact of various environmental factors. The aim of this work was to reveal the biological role of nitric oxide, its metabolic changes, and its mechanism of action in tissues under hypoxia, as well as the possibility of tissue metabolism correction through NO-dependent systems under the influence of Krebs cycle intermediates., Methods: A systematic assessment of the effect of succinate (SC, 50 mg/kg b.w.) and α-ketoglutarate (KGL, 50 mg/kg b.w.) in the regulation of oxygendependent processes in rats (mitochondrial oxidative phosphorylation, microsomal oxidation, intensity of lipid peroxidation processes, and the state of the antioxidant defense system) depending on functional changes in nitric oxide production during hypoxia was evaluated. The state of the nitric oxide system was estimated spectrophotometrically by determination of the concentration of its stable nitrite anion metabolite (NO 2 -). The levels of catecholamines were estimated from the content of epinephrine and norepinephrine using the differentially fluorescent method. The activity of cytochrome P450-dependent aminopyrine-N-demethylase was determined with the Nash reagent., Results: Tissue hypoxia and metabolic disorders caused by this condition through changes in the content of catecholamines (epinephrine, norepinephrine, dopamine, DOPA) as well as the cholinesterase-related system (acetylcholine content and acetylcholinesterase activity) were the studied experimental parameters under acute hypoxia (AH, 7% O 2 in N 2 , 30 min). The activation of lipid peroxidation and oxidatively modified proteins and an increase in the epinephrine content in AH are associated with an increased role of SC and a decrease in KGL as substrates of oxidation in mitochondria. A more pronounced effect of exogenous KGL, compared to SC, on the content of nitrite anion as a stable metabolite of nitric oxide in the liver under acute hypoxia against the background of a decrease in the intensity of lipid peroxidation processes was revealed. The activation of SC-dependent mitochondrial oxidative processes caused by AH was found to decrease in animals after an intermittent hypoxia training (IHT) course. IHT (7% O 2 in N 2 , 15-min, 5 times daily, 14 days) prevented the activation of oxidative stress in tissues and blood after the AH impact and increased the efficiency of energy-related reactions in the functioning of hepatic mitochondria through increased oxidation of KGL., Conclusion: The studied effects of adaptation are mediated by an increase in the role of NO-dependent mechanisms, as assessed by changes in the pool of nitrates, nitrites, carbamides, and total polyamines., Competing Interests: The authors have no conflicts of interest to declare., (© Copyright by the Author(s). Published by Cell Physiol Biochem Press.)

The review summarises the data of the last 50 years on the effectiveness of the amino acid L-arginine in therapeutic practice in conditions accompanied by different-origin hypoxia. The aim of this review was to analyse the literature and our research data on the role of nitric oxide in the modulation of individual physiological reactivity to hypoxia. The review considers the possibility of eliminating methodological conflicts in the case of L-arginine, which can be solved by taking into account individual physiological reactivity (or the hypoxia resistance factor). Considerable attention is paid to genetic and epigenetic mechanisms of adaptation to hypoxia and conditions of adaptation in different models. The article presents data on the clinical effectiveness of L-arginine in cardiovascular system diseases (hypertension, atherosclerosis, coronary heart disease, etc.) and stress disorders associated with these diseases. The review presents a generalised analysis of techniques, data on L-arginine use by athletes, and the ambiguous role of NO in the physiology and pathology of hypoxic states shown via nitric oxide synthesis. Data on the protective effects of adaptation in the formation of individual high reactivity in sportsmen are demonstrated. The review demonstrates a favourable effect of supplementation with L-arginine and its application depending on mitochondrial oxidative phosphorylation processes and biochemical indices in groups of individuals with low and high capacity of adaptation to hypoxia. In individuals with high initial anti-hypoxic reserves, these favourable effects are achieved by the blockade of NO-dependent biosynthesis pathways. Therefore, the methodological tasks of physiological experiments and the therapeutic consequences of treatment should include a component depending on the basic level of physiological reactivity.

Aims: Low-intensity infrared laser irradiation with output emissions of the laser and LED for in vitro irradiation of plasma and erythrocyte samples collected from healthy individuals and diabetes mellitus (DM) patients was used in the current study., Methods: The generated emission was in the range 0.85-0.89 nm with pulse duration near 130 ns and repetition rates of pulses 50, 150, 600, and 1500 Hz, average power 0, 50, or 100 mW, in the range of 1-9 min for different 30 variants of irradiation. The levels of 2-thiobarbituric-acid reactive substances (TBARS), aldehydic and ketonic derivatives of oxidatively modified proteins (OMP), total antioxidant capacity (TAC), acid-induced resistance of erythrocytes, and activities of the main antioxidant enzymes were assessed in erythrocyte and plasma samples after irradiation., Results: The low-intensity infrared laser irradiation and low-intensity light emitted by a red LED decreased the lipid peroxidation levels in the erythrocytes of both healthy individuals and DM patients. A statistically significant decrease in TBARS and OMP levels and an increase in the TAC level were observed at the irradiation energy of 34.39 and 68.79 J/cm 2 for samples collected from both healthy individuals and DM patients. The effects of the irradiation were accompanied by a statistically significant decrease in catalase activity of both healthy individuals and DM patients., Conclusions: In many variants of the laser irradiation and low-intensity light emitted by a red LED used in our study, a decrease in the percent of hemolyzed erythrocytes was observed, suggesting that laser therapy protocols should take into account fluencies, frequencies, and wavelengths of the laser before the beginning of treatment, especially in DM patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Based on studies of the wintering population of mute swans in large urban agglomerations, it is possible to identify and infer the impact of environmental pollution in coastal regions near Baltic Sea on the physiological and biochemical changes in the blood of waterfowls. Hematological and biochemical changes in the blood in relation to chemical elements in their feathers are a useful tool for general ecophysiological conclusions. Hematological changes and blood chemistry in Mute Swan Cygnus olor is particularly environmentally dependent, therefore we examined hematological picture (red blood cells RBC, white blood cells WBC, heterophiles, eosinophils, basophils, monocytes, lymphocytes, hemoglobin, heterophile to lymphocyte ratio H/L, biochemical indicators (glucose, uric acid, total cholesterol, triglycerides, calcium, inorganic phosphorus, magnesium, total protein), stability of erythrocyte membranes, concentration of Ca, P, Mg in the blood, concentration of Al, Zn, Rh, Cu, Ru, Fe, Pb in feathers, in wintering population of 172 mute swans of different age (juvenile, adult) and gender, in three coastal types of areas of Southern Polish zone of Baltic Sea (Słupsk, Gdynia, Sopot). Percentage of changes in the morphological indices in the blood of mute swans with three independent characteristics (environment, sex, age) revealed that hemoglobin content exhibited the highest value (R 2  = 53.8%) in the analysis of morphological indices; the effect of RBC, WBC, and basophils was much lower (WBC > RBC > basophils). Male and female erythrocytes from the coastal of Gdynia were more fragile than those of birds from coasts of Sopot and Słupsk. We found that osmotic fragility is altered in juvenile swans from Słupsk area and males from Gdynia area. The consequence was a higher level of hemolyzed erythrocytes in their blood. The effect of type of environment, age-, and sex-related impact on hematological indices and biomarkers of biochemical alterations in the blood of swans and comparison of these data with bioaccumulation of chemical elements in feathers of swans inhabiting 3 types of environment of Baltic coastal zone show significant differences in the hematological and biochemical indices. Albumins and globulins maintain the blood cations balance, however, changes in their concentrations in the blood suggest an impact on physiological mechanisms and body condition of swans., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The objective of the current study was to determine the photoperiod-induced variations and the impact of exercise on oxidative stress biomarkers [2-thiobarbituric acid reactive substances (TBARS), aldehydic (AD) and ketonic (KD) derivatives of oxidatively modified proteins (OMP), total antioxidant capacity (TAC), and activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)] and biomarkers of metabolic alterations [glucose, urea, and uric acid and the activity of lactate dehydrogenase (LDH)] in the blood of Shetland pony mares and stallions involved in recreational horseback riding. Twenty-one healthy adult Shetland ponies (11 mares and 10 stallions) aged 6.5 ± 1.4 years old from the central Pomeranian region in Poland were used in this study. Blood samples were taken once per season for one year: spring (3 April), summer (5 July), autumn (1 October) and winter (25 January). A MANOVA analysis revealed that the photoperiod factor had a leading role in alterations of these biomarkers, while the exercise and sex of the ponies exerted a lower impact. The lipid peroxidation biomarkers, for example, the plasma TBARS level, indicated the maximum adjusted coefficient of determination R 2 ad  = 0.77. Before exercise (at rest), the plasma of the stallions and mares exhibited minimum values of TBARS levels in the spring and summer photoperiods and maximum levels in autumn and winter. A statistically significant reduction in the levels of both aldehydic and ketonic derivatives of OMP in the blood of ponies was observed during the autumn and winter periods; additionally, the level of ketonic derivatives of OMP declined after exercise in spring. TAC was statistically significant in the spring and winter photoperiods both before and after exercise. SOD activity did not have a pronounced photoperiod-induced pattern but was dependent on the sex and exercise. CAT activity varied and was statistically significant only in the plasma of the mares after exercise in the spring, summer, and winter photoperiods. The minimum GPx activity in the blood of the mares before exercise (at rest) was observed in autumn, while the maximum was noted in winter and summer. Photoperiod- and exercise-induced alterations in markers of oxidative stress and antioxidant defences may contribute to the adaptation of animals to exercise, depending on sex. The seasonal variations in the antioxidant defences demonstrated in our study, as well as substrates of energy metabolism in the blood of mares and stallions, depending on exercise capacity, could be an important aspect in the ability of endogenous adaptive mechanisms of animals to react in advance to environmental changes associated with seasons.

An region of ecological hazard (EHR) is an area where, as a result of intensive human economic activity, degradation of components of the natural environment has taken place, leading to the deterioration of the ecological balance. EHR management is a globalised ever-increasing challenge. To eliminate the hazardous effect of these pollutants, research has been accelerated worldwide. The current study analyzed the specific biomarkers of the lipid and protein oxidation, total antioxidative status, activities of antioxidant enzymes (superoxide dismutase, catalase, glutathione reductase and peroxidase), lysosomal enzymes (alanyl aminopeptidase, leucyl aminopeptidase, acid phosphatase), and biomarkers of aerobic and anaerobic metabolic pathways (activities of alanine and aspartate aminotransferases, succinate dehydrogenase, lactate dehydrogenase, lactate and pyruvate levels) in skeletal muscle tissue of wild great tit nestlings in environments with different levels of anthropogenic pressure such as sodium industry and agriculture in the central part of northern Poland (Inowrocław EHR). Control samples were collected from Tuchola Forest and Borkowo village, where no direct sources of contamination were found. The relevance of the study was to assess the changes in lysosomal functioning caused by pollution-induced oxidative stress that may indicate multidirectional adaptative mechanisms of metabolic processes occurring in the wild birds to compensate for the negative effects of contamination. It was shown that the initiation of oxidative stress caused by anthropogenic pollution shifted the balance of the normal functioning of lysosomal enzymes towards their increased activity. A general tendency towards an increase in the intensity of lipid peroxidation processes with an increasing level of oxidatively modified proteins (aldehydic and ketonic derivatives) and a simultaneous reduction in the TAS was observed in the muscle tissue of great tits living in the anthropogenically modified areas. The intensity of lipid peroxidation and protein damage caused changes and reorganization of the energy-related metabolic pathways in the muscle tissue of wild great tits living in the sodium industry and agricultural areas of the EHR., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The intensification of oxidative stress and destabilization of the antioxidative defenses of an organism is a consequence of many environmental factors. We considered aspects conditioning male reproductive potential and the functionality of enzymatic antioxidative mechanisms, i.e., superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR), and their correlations with Li, Be, B, Na, Mg, Al, P, K, Ca, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Sr, Mo, Ag, Cd, Sn, Sb, Ba, Hg, Tl, Pb, and malondialdehyde (MDA), as well as genetic polymorphism IL-4 v. C589T (rs2243250) in men with infertility ( n = 76). A healthy normozoospermic control ( n = 87) was also used. We assessed the impact of negative changes driven by oxidative stress on enzymatic antioxidative mechanisms as well as the role of MDA in the overall process. On this basis, we infer connections between disturbances in enzymatic antioxidative defense and reproductive potential. Based on a molecular analysis of the polymorphism of gene IL-4 v. C589T (rs2243250) (chromosome 5) (PCR-RFLP), we considered the relationships among particular genotypes with the possibility of occurrence of male infertility. Concentrations of chemical elements were measured in the blood. The activity of antioxidants and MDA levels were measured in serum. In the infertile group, higher GPx activity was noted (6.56 nmoL·min -1 ·mL -1 , control: 4.31 nmoL·min -1 ·mL -1 ; p = 0.004), while GR achieved a greater level in the control (17.74 nmoL·min -1 ·mL -1 , infertile: 15.97 nmoL·min -1 ·mL -1 , p = 0.043), which implies diversified efficiency of the first and second lines of defense. The polymorphism of IL-4 v. C589T (rs2243250) was not directly connected with infertility because there were not any differences in the frequency of genotypes between the infertile and control group ( p = 0.578). An analysis of genotypes CC and TT (polymorphism IL-4 v. C589T (rs2243250)) indicated numerous correlations between antioxidants, chemical elements and MDA. Therefore, chemical economy, antioxidative defense and genetic conditions are connected and jointly shape male reproductive potential. Chemical elements influence antioxidative defense and male fertility; the most important modulators appeared to be Na, Ba, Al and B. The polymorphism of gene IL-4 v. C589T (rs2243250) has a limited influence on antioxidative defense and the metabolism of chemical elements.

The mute swan (Cygnus olor) can be considered a representative species of birds associated with the aquatic environment and responding very clearly to changes in the environment. Assuming that the condition of the mute swan population well reflects the state of the environment, this species was used in our research as a bioindicative species. Thus, the aim of our study was to elucidate the association between metal contents in soil samples collected from a habitat of mute swans and element contents in their feathers as well as the levels of biomarkers of lipid peroxidation, oxidatively modified proteins, and total antioxidant capacity in the blood of mute swans living in three agglomerations in coastal areas in the southern part of the Baltic Sea (Pomeranian region, northern Poland). We compared the effects of inhabitation, age, and sex on the ecophysiological accumulation of metals in three wintering populations of the mute swan from coastal areas of northern Poland, i.e., Słupsk, Gdynia, and Sopot. In Słupsk, the anthropogenic pressure was related predominantly to the level of Al and, to a lesser extent, to the content of Rh and Ru. We found maximum levels of lipid peroxidation biomarkers in the blood of the mute swans from Gdynia (38.20 ± 6.35 nmol MDA·mL -1 ). At the same time, maximum levels of aldehydic and ketonic derivatives of oxidatively modified proteins were noted in the blood of swans from Sopot compared to the values obtained in mute swans from Słupsk and Gdynia. This trend suggesting high levels of oxidative stress biomarkers was also confirmed by a decrease in the total antioxidant capacity in these groups., (© 2021. The Author(s).)

Imbalanced glucose tolerance and insulin resistance remain important as high cancer risk factors. Metformin administration to diabetic patients may be associated with a reduced risk of malignancy. The combined effects of the hormone melatonin and metformin in oncology practice have shown positive results. The relevance of our study is to find out the role of specific biomarkers of lysosome destruction and oxidative stress data in carcinogenesis models. The present study was designed to investigate the comparative synergic effect of peroral antidiabetic metformin (MF) and pineal hormone melatonin (MEL) administered alone and in combination in two different rat's models of mammary tumour proliferation in vivo (N-methyl-N-nitrosourea, NMU or 7,12-dimethylbenz[a]anthracene, DMBA). We have studied the processes of lysosomal destruction (alanyl aminopeptidase AAP, leucyl aminopeptidase LAP, acid phosphatase AcP, β-N-acetylglucosaminidase NAG, β-galactosidase β-GD and β-glucuronidase β-GR) caused by evaluated oxidative stress in three types of tissues (liver, heart, and spleen) in female Sprague-Dawley rats fed a high-fat diet (10% of total fat: 2.5% from lard and 7.5% from palm olein). Our results revealed an increase in the activity of the studied lysosomal enzymes and their expression in a tissue-specific manner depending on the type of chemical agent (NMU or DMBA). MANOVA tests in our study confirmed the influence of the three main factors, type of tissue, chemical impact, and chemopreventive agents, and the combinations of these factors on the lysosomal activity induced during the process of cancerogenesis. The development and induction of the carcinogenesis process in the different rat models with the high-fat diet impact were also accompanied by initiation of free-radical oxidation processes, which we studied at the initial (estimated by the level of diene conjugates) and final (TBARS products) stages of this process. The combined effects of MEL and MF for the two models of carcinogenesis at high-fat diet impact for AAP, LAP, and AcP showed a significant synergistic effect when they impact together when compared with the effects of one substance alone (either MEL or MF) in the breast cancer model experiments. Synergistic effects of limiting destructive processes of lysosomal functioning β-GD enzyme activity we obtained in experiments with MEL and MF chemoprevention for both models of carcinogenesis for three tissues. The statistical SS test allowed us to draw the following conclusions on the role of each lysosomal parameter analyzed as an integral model: NAG > AcP > β-GD > β-GR > AAP > LAP., (© 2022. The Author(s).)

The current study aimed to identify correlative and regressive dependencies between the water iodine concentration and the levels of TSH (thyroid-stimulating hormone), thyroglobulin antibodies (TgAbs), and thyroid peroxidase (TPOAb) in the serum of 168 in patients (34 men and 134 women) with a hypothyroid form of Hashimoto's thyroiditis who use water from the supply network and individual wells. Based on the water iodine concentration, low and moderate degrees of iodine endemia in the location of the patients were determined. In the groups of men and women using water from different water supply sources, there were direct correlations between the water iodine concentrations and the TgAbs and TPOAb titers as well as an inverse dependence between iodine and TSH levels. Multivariate regressive analysis indicated that TgAb and TSH in the group of women using water from a supply network and TPOAb titers in the group of women using well water were independent factors associated with water iodine concentrations. Statistically significant correlations and regressive dependencies between the water iodine concentrations and the biomarkers of the thyroid status of the patients indicate the risk of Hashimoto's thyroiditis progression, especially among women with additional iodine intake., (© 2021. The Author(s).)

Effects of photoperiodicity caused by both the age and individual physiological reactivity estimated by resistance to hypobaric hypoxia on the levels of lipid peroxidation, protein oxidation (aldehydic and ketonic derivatives), total antioxidant capacity, activities of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase), and biochemical parameters of aerobic and anaerobic pathways in hepatic tissue depending on the blood melatonin level were studied. The study was carried out on 96 6- and 21-month-old male rats divided into hypoxia resistance groups (LR, low resistance, HR, high resistance). The analyses were conducted at four photoperiods: winter (January), spring (March), summer (July), and autumn (October). Our results indicate a significant effect of melatonin, i.e. over 80%, revealed by the complete statistical model of the studied biomarkers of oxidative stress and oxygen-dependent parameters of metabolism. The effects of melatonin vary with age and between photoperiods, which in turn was determined by individual physiological reactivity. In terms of the photoperiods, the melatonin content in the group of the adult animals with low resistance to hypoxia decreased from winter to summer. In a group of old animals in comparison with adults, the melatonin content in all the studied photoperiods was much lower as well, regardless of their hypoxia resistance. In the group of old animals with low resistance to hypoxia, the melatonin content decreased throughout the photoperiods as follows: winter, autumn, summer, and spring. As can be concluded, spring is a critical period for old animals, particularly those with low hypoxia resistance. The important role of melatonin in these processes was also confirmed by our correlation analysis between oxidative stress biomarkers, energy-related metabolites, and antioxidant enzymes in the hepatic tissue of rats of different ages, with different resistance to hypoxia, and in different photoperiods. The melatonin concentration in the blood of highly resistant rats was higher than in those with low resistance to hypoxia. Melatonin determines the individual constitutional level of resistance to hypoxia and is responsible for individual enzymatic antioxidative responses, depending on the four photoperiods. Our studies have shown that melatonin levels are related to the redox characteristics of antioxidant defenses against lipid peroxidation and oxidative modification of proteins in old rats with low resistance to hypoxia, compared to a group of highly resistant adults. Finally, the melatonin-related mechanisms of antioxidative protection depend on metabolic processes in hepatic tissue and exhibit photoperiodical variability in adult and old rats.

The aim of the present study was to evaluate the biochemical responses of the skeletal muscle and cardiac tissues of the urban pigeon as a bioindicator organism tested in diverse environments (Szpęgawa as a rural environment and Słupsk as an urban environment, Pomeranian Voivodeship, northern Poland), resulting in changes in the level of lipid peroxidation at the initial and final stages of this process and the activities of Krebs cycle enzymes (succinate dehydrogenase, pyruvate dehydrogenase, isocitrate dehydrogenase, and alfa-ketoglutarate dehydrogenase). Szpęgawa village was chosen due to the intensive use of the European motorway A1 with significant traffic and pollution levels. The concentration of Pb was higher in the soil and feathers of pigeons nesting in the polluted areas (Szpęgawa). Our studies have shown that the presence of lead in soil and feathers of the pigeons resulted in the activation of lipid peroxidation, destabilization and increased activity of lysosomal membranes, and activation of mitochondrial enzymes of the Krebs cycle with energy deficiency (reduction of ATP levels) in cardiac and skeletal muscle tissues simultaneously., (© 2021. The Author(s).)

The present study examines the effects of natural infection by small ruminant lentivirus (SRLV) in the two most common goat breeds in Poland, i.e., Polish white improved and polish fawn improved. It focuses on biomarkers of oxidative stress, oxidatively modified proteins and antioxidant defenses, ceruloplasmin level as an acute phase protein, and the activities of antioxidant enzymes in the goat serum. It was conducted on 24 goats divided into two equal groups: one SRLV-seropositive (SRLV-SP) and another SRLV-seronegative (SRLV-SN). Both groups were identical in terms of breed and parity. Despite infection, the SRLV-SP goats demonstrated no symptoms of caprine arthritis-encephalitis. In addition, the SRLV-SP goats did not reveal pronounced dysfunctions in oxidative stress biomarkers in the serum compared to the SRLV-SN animals. However, both groups demonstrated elevated levels of the aldehydic and ketonic derivatives of oxidatively modified proteins during the lactation period. In addition, both groups retained a high total antioxidant capacity in serum despite the decrease of enzyme antioxidant defenses throughout the 200-day lactation period.

Background: The goal of this study was to assess the effect of melatonin on blood redox systems in mice simultaneously exposed to ethanol and low-dose lipopolysaccharide (LPS)., Methods: Oxidative stress parameters were assessed in eight groups: untreated control, melatonin (10 mg kg -1 , 10 days), LPS (injected once intraperitoneally at a dose of 150 μg per mouse), LPS with previous melatonin treatment, acute ethanol-induced stress (AES, 0.75 g kg -1 per day, 10 days), AES with previous melatonin treatment, LPS- and AES-induced toxicity, and melatonin treatment., Results: Both ethanol and LPS induced oxidative stress. The combination of these two factors was even more toxic to the organism. Melatonin stabilized erythrocyte membranes and decreased the high level of free radical oxidation at the initial and final stages. Furthermore, melatonin limited protein damage through maintenance in the functional ability of the blood redox system to counteract pathological conditions., Conclusions: Melatonin limited the negative effects associated with alcohol consumption and low-intensity inflammation.

Investigation of the pathogenesis of alcoholism in humans using different methodological approaches has facilitated detection of important biological factors of consequent metabolic diseases, endocrine disorders, and other medical conditions, such as alcoholic cardiomyopathy, alcoholic hypertension, heart and vascular lesions, alcoholic liver disease, alcoholic pancreatitis, etc. Alcohol abuse leads to damage to the nervous system, which can result in neurological and mental disorders, including alcoholic polyneuropathy, psychosis, and alcohol dementia. The complexity and versatility of the harmful effects of regular alcohol consumption on the human body can be considered in the perspective of a chronobiological approach, because alcohol is chronotoxic to biological processes. As a rhythm regulator, melatonin exerts a wide range of different effects: circadian rhythm regulation, thermoregulation, sleep induction, antioxidant, immunomodulatory, and anti-stress ones. This review presents from a chronobiological perspective the impact of melatonin on alcohol intoxication in terms of mental disorders, sleep and inflammation, hepatic injury, and mitochondrial function. It discusses the main clinical effects of melatonin on alcohol injury and the main targets as a therapy for alcohol disorders. Chronobiological effects of ethanol are related to melatonin suppression that has been associated with, among others, cancer risk. Exogenous melatonin seems to be a promising hepato- and immune-protector due to its antioxidant and anti-inflammatory properties, which in combination with other medicines makes it useful to prevent alcoholic organ damage. The reason for the scientific interest in melatonin as a treatment for alcoholism is obvious; the number of cases of this pathology that gives rise to metabolic syndrome, and its subsequent transformation into steatohepatitis, liver fibrosis, and cirrhosis, is increasing worldwide. Melatonin not only exerts antioxidant effects but it exerts various other effects contributing to the management of liver conditions. This review discusses the interaction between normal and pathological processes caused by alcohol consumption and the relationship between alcohol and melatonin in these conditions.

This study evaluated a prolonged effect of palm oil addition to lard-supplemented diet (PLD) on the oxidative status, lysosomal enzyme activities, markers of hepatotoxicity and basic lipid profile in female rats. Female Sprague-Dawley rats received PLD (10% of total fat: 7.5% from palm oil and 2.5% from lard), and the control group received lard-supplemented diet (2.5% fat) from 28 days of age for 14 weeks. Histopathological evaluation of the liver from animals fed the PLD showed slight steatosis and signs of mild chronic inflammation. Reduction of extramedullary hematopoiesis and an increased ratio of red/white pulp were observed in the spleen. PLD induced oxidative stress (evaluated in the liver, heart, spleen, muscle and kidney) evidenced by an increase in conjugated dienes and malondialdehyde in all tissues except the muscle; protein carbonyl derivatives were increased as well. The changes in the antioxidant enzyme activities in the evaluated tissues were ambiguous except for the prominent increase in the heart. Lysosomal enzyme activities showed a tendency to increase in the heart and kidney and to decrease in the muscle and spleen. The De Ritis ratio, which is a biomarker of hepatotoxicity, was higher in the heart from animals fed the PLD. The palm oil addition to the lard-supplemented diet-induced prominent oxidative stress, particularly in myocardial tissue with involvement of the authophagy-lysosome pathway., (© 2020 Wiley-VCH GmbH.)

The study aimed to assess the levels of trace elements, minerals, and toxic elements as well as lipid peroxidation biomarkers (lipid acyl hydroperoxides, 2-thiobarbituric acid reactive substances (TBARS)) in the blood of children with chronic fluorosis from endemic fluorosis areas (Sosnivka village, Lviv region, western Ukraine). The results were compared with healthy children from Staryi Sambir (Lviv region, western Ukraine), whose drinking water contained permissible levels (< 1 ppm) of fluoride. Thirty-one children from the Sosnivka village in the Lviv region, including 16 females and 15 males aged 7-10 years, with clinically diagnosed fluorosis, were recruited for the study. The children had been exposed to fluoride (> 1.5 ppm) through drinking water for more than 5 years. In the blood, eight macro- and microelements (calcium, zinc, potassium, iron, copper, selenium, manganese, chromium), five additional elements (sulfur, bromine, chlorine, nickel, strontium), and four toxic elements (lead, mercury, cadmium, mercury) were assessed with the X-ray fluorescence method. The results of our study demonstrated a 14-fold decrease in the copper level, a 2.5-fold decrease in the calcium and zinc levels, and a 2-fold decrease in the selenium level in the blood of children with chronic fluorosis compared with the healthy children from the non-fluorosis area. In turn, a 1.7- and 1.4-fold increase in the strontium and lead content, respectively, was noted. The sulfur, chlorine, potassium, calcium, copper, zinc, and selenium levels in the blood samples of children with chronic fluorosis were lower than the reference value. The children had higher blood TBARS levels, while the acyl hydroperoxide levels were non-significantly increased in comparison with healthy children living in the non-fluorosis area. Additionally, the bromine level was correlated positively with the selenium level and acyl hydroperoxides. However, more studies are needed to clarify the relationship between blood mineral status, oxidative stress biomarkers, and chronic fluorosis.

Pigeons can be successfully used as bioindicators of a contaminated environment. We studied the relationship between the functioning of the pro/antioxidant balance in muscle tissues (skeletal muscle and cardiac tissues) of pigeons (Columba livia f. urbana) living in areas with different levels of pollution (Pomeranian Voivodeship, Northern Poland). The current study demonstrated the impact of the environment with preferential high Pb contamination in soil and feathers of pigeons on the formation of adaptive redox mechanisms in muscle tissues. An increase in the intensity of lipid peroxidation (estimated by the TBARS level) accompanied by enhancement of the oxidative modification of proteins (aldehydic and ketonic derivatives) and an important decrease in the activity of antioxidant enzymes (SOD, CAT, and GR) in pigeon muscle tissue was observed. These changes in enzyme activities were dependent on the type of muscle tissue (skeletal muscle and cardiac tissues). Our results confirm the concept of the recalculation of the De Ritis ratio (AsAT/AlAT) in both types of muscles indicating the tendency to cardio- and hepatocellular damage and toxicity caused by heavy metals from the polluted environment.

Common carp ( Cyprinus carpio ) is one of the most important cultured fish species in Poland. The aims of our study were to determine the concentration of essential minerals in the muscle tissue of carp obtained from a pond culture and to compare the content of these minerals with the physiological norms of nutrition for the Polish population, Recommended Dietary Allowances (RDA), and Estimated Average Requirements (EAR). The non-carcinogenic and carcinogenic risk by assessment of the Estimated target hazard quotients (THQ), total target hazard quotients (ΣTHQ), and carcinogenic risk were also studied. The muscle tissue of the carp was rich in macroelements. The pattern significance gradation of element concentrations was as follows: Na > K > Ca > P > Mg > Al > Zn > Fe > Cu > Mn > Cr > Se > Co. The concentration of toxic heavy metals in the samples was lower than the maximum allowable level of metals in food products. The risk of consumption of toxicants by an adult at a daily intake of 100 g of fish was 1.45% for Pb, 0.1% for Hg, 0.02% for Cd, and 0.02% for As, compared to the allowable daily intake for each toxicant. The value of the target hazard quotients of each metal was less than 1, indicating that the intake of a single metal through the consumption of carp meat does not pose a considerable health hazard. The total value of the target hazard quotients was also less than 1, indicating the safety of the combined effects of the chemicals. The major risk contributor was Pb with 82.9%, followed by Hg (9.38%), As (6.43%), and Cd (1.29%)., Competing Interests: Conflict of interestNone declared., (© The Author(s) 2021.)

The aim of our study was to elucidate the effects of both development stages (parr, smolt, adult, spawner), and kelt as a survival form and sex (male, female) on the functional stability of the lysosomal complex, biomarkers of oxidative stress, and element contents in the muscle tissue of the sea trout (Salmo trutta m. trutta L.) sampled in the Pomerania region (northern Poland). We have evaluated the maximal activities of lysosomal enzymes (alanyl aminopeptidase, leucyl aminopeptidase, β-N-acetylglucosaminidase, and acid phosphatase), lipid peroxidation level, and protein carbonyl derivatives as indices of muscle tissue degradation. The relationship between lysosomal activity and oxidative stress biomarkers estimated by the lipid peroxidation level and protein carbonyl derivatives was also assessed, as well as the relationships between element levels and oxidative stress biomarkers. Trends of the main effects (i.e., the development stages and sex alone, the interaction of the sex and development stage simultaneously) on oxidative stress biomarkers, lysosomal functioning, and element contents in the muscle tissue were evaluated. The study has shown sex-related relationships between the pro- and antioxidant balance and the tissue type in the adult stage as well as modifications in the lysosomal functioning induced by long-term environmental stress associated with changing the habitats from freshwater to seawater and intense migrations. The highest level of toxic products generated in oxidative reactions and oxidative modification of proteins was noted in both the spawner stage and the kelt form. The holistic model of analysis of all parameters of antioxidant defense in all development stages and sex demonstrated the following dependencies for the level of lipid peroxidation, oxidative modification of proteins, lysosomal activities, and element contents: TBARS > OMP KD > OMP AD > TAC, AcP > NAG > LAP > AAP and Cu > Fe > Ca > Mn > Zn > Mg, respectively.

Introduction: The most frequently isolated bacteria in Polish aquaculture are of the Aeromonas genus; also pathogenic to human fish consumers, they cause substantial economic losses, and require antibiotic therapy to treat. Antibiotic residues in animal-derived food provoke concern. The aim of the study was to appraise the antimicrobial activity of ethanolic extracts of Ficus plant species against Aeromonas strains., Material and Methods: Leaves of 41 Ficus species were collected from two Ukrainian botanic gardens. They were crushed, washed, homogenized in ethanol and centrifuged, and the supernatants were applied in the Kirby-Bauer disc-diffusion method to assess the susceptibility to them of Aeromonas hydrophila , A. sobria , and A. salmonicia subsp. salmonicida isolates confirmed as K886, K825, and St30 strains. Analogous assessment was also made of these bacteria's susceptibility to sulfonamides, quinolones, tetracyclines, and one amphenicol. Data were analysed statistically., Results: The majority of the extracts considerably inhibited bacterial growth, A. sobria being susceptible to 14 Ficus species, A. salmonicida subsp. salmonicida to 13, and A. hydrophila to 10., Conclusion: Treatment with plant extracts has promise as an alternative to antibiotic therapy. Botanic gardens may offer new sources of plant-derived agents with a broad spectrum of biological and antimicrobial action. Further research will be useful to broaden knowledge of Ficus' therapeutic potential., Competing Interests: Conflict of Interest Conflict of Interests Statement: The authors declare that there is no conflict of interests regarding the publication of this article., (© 2021 A. Pękala-Safińska et al. published by Sciendo.)

The study establishes a link between alcoholism, inflammation state, and melatonin synthesis. The aim of our study was to evaluate the effects of melatonin on changes in the relationships between oxygen consumption (using NADH- or FAD-generated substrates of mitochondrial respiration), activities of lysosomal enzymes, such as alanyl aminopeptidase (AAP), leucyl aminopeptidase (LAP), β-N-acetylglucosaminidase (NAG), and acid phosphatase (AcP), biomarkers of oxidative stress estimated by the 2-thiobarbituric acid reactive substance (TBARS) level as a biomarker of lipid peroxidation, carbonyl derivatives as biomarkers of oxidatively protein damage, and biomarkers of energy metabolism during acute ethanol-induced stress (AES), and a low-dose lipopolysaccharide (LPS)-induced inflammatory responses in mice. Biochemical assays of lysosomal enzymes, biomarkers of oxidative stress, and parameters of energy metabolism (activities of alanine- and aspartate aminotransferases, succinate dehydrogenase, levels of lactate and pyruvate) were carried out in eight groups: 1) untreated control, 2) melatonin treatment (Mel, 10 mg/kg b.w., 10 days), 3) acute ethanol-induced stress (AES, 0.75 g/kg b.w., 10 days), 4) AES model with previous Mel treatment (10 mg/kg b.w., 10 days), 5) LPS-induced inflammation (injected once intraperitoneally, 150 μg/mouse), 6) LPS-induced inflammation with previous Mel treatment (10 mg/kg b.w., 10 days), 7) LPS-induced inflammation with AES model, 8) LPS-induced inflammation with AES model and Mel treatment (10 mg/kg b.w., 10 days). Oxidative stress caused by acute ethanol-induced intoxication and low-dose LPS-induced inflammation lead to structural and functional impairments, with alterations in oxygen consumption more prominent in kidneys than liver. Melatonin treatment had significant effects on mitochondrial oxidation of the NADH-generated substrate, and it also decreased mitochondrial ability to oxidize FAD-generated substrate and mitochondrial coupling in both LPS- and AES-induced oxidative stress. Melatonin exerts significant effect on the oxidation of the NAD-generated substrates. The increased lipid peroxidation and De Ritis ratio suggest damage to intracellular membrane integrity with combined effects of ethanol and LPS-induced toxicity, which can potentially result in irreversible tissue damage. Melatonin prevents lysosomal destruction of liver tissue and, to greater extent, kidney tissue during AES with simultaneous LPS exposure by limiting increased activity of lysosomal enzymes and resulting oxidative stress.

This review concerns the current knowledge of melatonin and alcohol-related disorders. Chronobiological effects of ethanol are related to melatonin suppression and in relation to inflammation, stress, free radical scavenging, autophagy and cancer risk. It is postulated that both alcohol- and inflammation-induced production of reactive oxygen species (ROS) alters cell membrane properties leading to tissue dysfunction and, subsequent further ROS production. Lysosomal enzymes are often used to assess the relationships between intensified inflammation states caused by alcohol abuse and oxidative stress as well as level of tissue damage estimated by the increased release of cellular enzymes into the extracellular space. Studies have established a link between alcoholism and desynchronosis (circadian disruption). Desynchronosis results from the disorganization of the body's circadian time structure and is an aspect of the pathology of chronic alcohol intoxication. The inflammatory conditions and the activity of lysosomal enzymes in acute alcohol poisoning or chronic alcohol-dependent diseases are in most cases interrelated. Inflammation can increase the activity of lysosomal enzymes, which can be regarded as a marker of lysosomal dysfunction and abnormal cellular integrity. Studies show alcohol toxicity is modulated by the melatonin (Mel) circadian rhythm. This hormone, produced by the pineal gland, is the main regulator of 24 h (sleep-wake cycle) and seasonal biorhythms. Mel exhibits antioxidant properties and may be useful in the prevention of oxidative stress reactions known to be responsible for alcohol-related diseases. Naturally produced Mel and exogenous sources in food can act in free radical reactions and activate the endogenous defense system. Mel plays an important role in the normalization of the post-stress state by its influence on neurotransmitter systems and the synchronization of circadian rhythms. Acting simultaneously on the neuroendocrine and immune systems, Mel optimizes homeostasis and provides protection against stress. Abbreviations: ROS, reactive oxygen species; Mel, melatonin; SRV, resveratrol; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; ANT, arylalkylamine-N-acetyltransferase; EC cells, gastrointestinal enterochromaffin cells; MT1, melatonin high-affinity nanomolecular receptor site; MT2, melatonin low-affinity nanomolecular receptor site; ROR/RZR, orphan nuclear retinoid receptors; SOD, superoxide dismutase; CAT, catalase; GPx, glutathione peroxidase; GR, glutathione reductase; GSH, reduced form of glutathione; GSSG, oxidized form of glutathione; TAC, total antioxidant capacity; ONOO∙ - , peroxynitrite radical; NCAM, neural cell adhesion molecules; LPO, lipid peroxidation; α-KG, α-ketoglutarate, HIF-1α, Hypoxia-inducible factor 1 -α , IL-2, interleukin-2; HPA axis, hypothalamic-pituitary-adrenal axis; Tph1, tryptophan hydroxylase 1; AA-NAT, arylalkylamine-N-acetyltransferase; AS-MT, acetylserotonin O-methyltransferase; NAG, N-acetyl-beta-D-glucosaminidase; HBA1c glycated hemoglobin; LPS, lipopolysaccharide; AAP, alanyl-aminopeptidase; β-GR, β-glucuronidase; β-GD, β-galactosidase; LAP, leucine aminopeptidase.

High-altitude intolerance and consequently high-altitude sickness, is difficult to predict. Liver is an essential organ in glucose and lipid metabolism, and may play key role in the adaptation to high altitude. In response to extreme high altitude, mitochondrial respiration exhibits changes in substrate metabolism, mitochondrial electron transport chain activity, and respiratory coupling. We determined the cobalt chloride (CoCl 2 ) effects on liver mitochondrial plasticity and oxygen uptake in rats with low resistance (LR) and high resistance (HR) to extreme hypobaric hypoxia. The polarographic method proposed by Chance and Williams was used as a simple and effective tool to trace mitochondrial functionality and oxygen consumption. HR rats had more efficient processes of NADH- and FAD-generated mitochondrial oxidation. CoCl 2 promoted more efficient NADH-generated and diminished less efficient FAD-generated mitochondrial respiratory reactions in HR rats. CoCl 2 diminished both aerobic and anaerobic processes in LR rats. Glutamate and pyruvate substrates of NADH-generated mitochondrial pathways were highly affected by CoCl 2 . Red blood cells acted as cobalt depots in HR and LR rats. We have unveiled several mechanisms leading to differentiated mitochondrial respiratory responses to hypobaric hypoxia in LR and HR rats. Our study strongly supports the existence of adaptive liver mitochondrial plasticity to extreme hypoxia.

Objectives: We tested the hypothesis that computed tomography (CT) perfusion markers of cerebral microcirculation would improve 36 months after internal carotid artery stenting for symptomatic carotid stenosis while results obtained 6-8 weeks after the stenting procedure would yield a predictive value., Methods: We recruited consecutive eligible patients with >70% symptomatic carotid stenosis with a complete circle of Willis and normal vertebral arteries to the observational cohort study. We detected changes in the cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), time to peak (TTP) and permeability surface area-product (PS) before and after carotid stenting. We have also compared the absolute differences in the ipsilateral and contralateral CT perfusion markers before and after stenting. The search for regression models of "36 months after stenting" results was based on a stepwise analysis with bidirectional elimination method., Results: A total of 34 patients completed the 36 months follow-up (15 females, mean age of 69.68±S.D. 7.61 years). At 36 months after stenting, the absolute values for CT perfusion markers had improved: CBF (ipsilateral: +7.76%, contralateral: +0.95%); CBV (ipsilateral: +5.13%, contralateral: +3.00%); MTT (ipsilateral: -12.90%; contralateral: -5.63%); TTP (ipsilateral: -2.10%, contralateral: -4.73%) and PS (ipsilateral: -35.21%, contralateral: -35.45%). MTT assessed 6-8 weeks after stenting predicted the MTT value 36 months after stenting (ipsilateral: R2=0.867, contralateral R2=0.688)., Conclusions: We have demonstrated improvements in CT perfusion markers of cerebral microcirculation health that persist for at least 3 years after carotid artery stenting in symptomatic patients. MTT assessed 6-8 weeks after stenting yields a predictive value.

Using a stage- and sex-based multivariate significance tests on the sea trout Salmo trutta m. trutta L. model, we show dependencies in the balance between lipid peroxidation processes, levels of carbonyl derivatives, and activity of antioxidant enzymes (superoxide dismutase SOD, catalase CAT, glutathione reductase GR, and peroxidase GPx) in the processes of antioxidant profile formation during the fish growing process. The study was aimed at examination of the relationships between the biomarkers of oxidative stress estimated by the total antioxidant status as well as the dependencies between the sex (male, female) and developmental stage of the wild sea trout from the Slupia River and its catchment area rivers. Functioning of the pro/antioxidant balance of the liver tissue reflected the course of the individual developmental stages of the trout and was associated with significant intensification of lipoperoxidation, oxidative modification of proteins, and reduction of the total antioxidant capacity of fish along with age. Formation of a holistic model for the analysis of the involvement of all parameters of antioxidant protection in all stages of development and sex allowed us to obtain the following rank order for the level of lipoperoxidation processes, modified proteins, and antioxidant enzyme complex: CAT > SOD > GPx > GR and TBARS > OMP KD > TAC > OMP AD., (Copyright © 2019 The Author. Published by Elsevier GmbH.. All rights reserved.)

Lipopolysaccharide (LPS) administration in an in vivo experimental mice model causes oxidative damage in the liver, muscle, and kidney. We aimed to determine specific mechanisms underlying melatonin's antioxidant protective role. Assays were carried out in quadruplicate in the control, melatonin (10 mg/kg, 10 days), acute LPS administration (once 150 μg), and LPS + melatonin groups. LPS stimulated lipid peroxidation processes (dienes and malondialdehyde) and antioxidant enzyme concentrations (superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase) were assessed in all investigated tissues. Protein oxidation processes (measured as aldehyde and kenotic carbonyl protein derivatives) were enhanced by LPS in the kidney and liver but not in muscle. Melatonin reversed LPS-induced changes, with the exception of muscle protein oxidation. LPS-induced oxidative stress resulted in augmented early-stage diene conjugated and end-stage malondialdehyde lipid peroxidation processes and affected antioxidant activity in liver, kidney, and muscle tissues. LPS activated protein oxidation processes in the kidney and liver. Melatonin ameliorated oxidative damage in the liver, kidney, and partially in the muscle. Melatonin modulates oxidative stress-induced states. Potential synergism between melatonin and systemic inflammation in terms of oxidative modification of muscle proteins needs to be clarified in further studies.

The aim of the study was to elucidate the effects of melatonin administration (10 mg/kg, 10 days) in a model of inflammation and oxidative stress induced by low-dose bacterial lipopolysaccharide (LPS, once 150 μg). Assays were carried out in quadruplicate in the control, melatonin (10 mg/kg, 10 days), acute LPS administration (once 150 μg) and LPS plus melatonin groups. Blood morphological examination was performed. Erythrocyte resistance to haemolytic agents, ceruloplasmin, diene conjugates, malondialdehyde, oxidatively modified protein concentrations, total antioxidant capacity and antioxidant enzyme activity in plasma were measured. LPS administration in mice resulted in white blood cell (WBC) depletion, erythrocyte cell membrane impairment and oxidative stress in plasma characterised by lipid and protein oxidative processes, decreased antioxidative defence and augmented ceruloplasmin concentrations. Melatonin treatment provided to LPS-exposed animals restored WBC counts, ameliorated erythrocyte membrane damage and decreased overall oxidative stress in plasma. Melatonin provides multilevel protection in animals exposed to low-dose LPS.

Oxidative stress is involved in the development of various cancers. In the present study, the effect of long-term administration of peroral antidiabetic metformin and pineal hormone melatonin on liver antioxidant and aerobic status in female Sprague-Dawley rats carrying mammary tumors induced by N-methyl-N-nitrosourea was evaluated. Both substances were administered in a preventive and curative manner (12 days before and 16 weeks after the carcinogen application). Carcinogen administration induced oxidative stress: the level of thiobarbituric acid reactive substances (TBARS) considered as a marker of reactive oxygen species (ROS) generation in liver increased as well as the level of oxidatively modified protein content (OMP; aldehyde and ketone derivates). Metformin administration restored succinate dehydrogenase and lactate dehydrogenase activity and associated ROS production and OMP content to the level of intact rats, with predominant activation of superoxide dismutase (SOD) and glutathione reductase (GR). Melatonin alone and in combination with metformin also decreased TBARS content. OMP content decreased in all groups receiving chemoprevention. The rise in total antioxidant capacity after melatonin and particularly metformin and melatonin combination might result from the initiation of anaerobic metabolism and increasing SOD, GR, and glutathione peroxidase activity. Long-term administration of metformin and melatonin exerts antioxidant properties in liver, especially in combination.

The aim of this study was to determine the effects of long-term administration of the oral antidiabetic metformin or the pineal hormone melatonin, and a combination thereof, in preventing oxidative stress in the heart tissue of female Sprague-Dawley rats with mammary tumors induced by N-methyl-N-nitrosourea (NMU) (50 mg/kg) given on the 42nd postnatal day. Metformin and melatonin were administered 12 days before and 16 weeks after the carcinogen. During the experiment, all animals were fed a high fat diet (10% total fat, 2.5% from lard, and 7.5% from palm oil). The findings are that mammary carcinogenesis generated oxidative stress. Reactive oxygen species (ROS) content, estimated from thiobarbituric acid reactive substances (TBARS), oxidatively modified protein content (aldehyde and ketone derivatives), and the activity of the antioxidant enzymes superoxide dismutase, glutathione reductase, and glutathione peroxidase were all augmented. Metformin caused a decrease in oxidative stress in the heart, accompanied by a decrease in diene conjugates, the elimination of ROS (stable total antioxidant status), and the activation of catalase and glutathione reductase. Melatonin caused an increase in total antioxidant status and a substantial reduction in ROS as estimated from aldehyde and ketone derivatives, lipid peroxidation at the initial (diene conjugates) and terminal stages (TBARS), and increased catalase and glutathione peroxidase activities. Metformin and melatonin combined reversed the effects of NMU on oxidative stress. In conclusion, melatonin reduces the level of oxidative stress in the heart tissue, caused by NMU carcinogenesis and a high fat diet, significantly stronger than metformin.

Aims: The aim of the study was to examine the effects of melatonin impact on changes in haematological profile, biomarkers of oxidative stress (dienes conjugates, malondialdehyde (MDA), oxidatively modified protein levels, total antioxidant capacity and antioxidant enzyme activity) in liver, muscle, kidney and erythrocytes, and glycated haemoglobin (HBA1c) in mice during acute ethanol stress., Methods: Assays were carried out in quadruplicate: control, melatonin (10 mg/kg, 10 days), acute ethanol stress (0.75 g/kg/day, 10 days) and acute ethanol stress plus melatonin groups., Results: Acute ethanol stress caused a significant increase in the total number of white blood cells (WBC), especially neutrophils in the blood, and HBA1c levels vs. control mice. The correlation between lipid peroxidation and the glycated haemoglobin level was shown (r = 0.93, P = 0.007). Ethanol reduced the antioxidant capacity by increasing reactive oxygen species (ROS) production and the level of oxidatively modified protein content, diene conjugates and MDA. Melatonin administration in animals during acute ethanol stress reduced antioxidant stress biomarkers, WBC, HBA1c levels and ROS production., Conclusions: Melatonin had protective effects on liver, kidney and muscle tissues by preventing the intensive lipid peroxidation processes in initial (diene conjugation production) and late stages (MDA level), and significantly reduced the level of aldehyde and ketone protein derivatives. Furthermore, melatonin restored elevated WBC count and HBA1c level and diminished ROS production., Short Summary: Ethanol reduces antioxidant capacity and leads to exaggerated reactive oxygen species production and consequent increases in oxidatively modified proteins. Melatonin exerts protective effects by preventing the intensive lipid peroxidation processes. Melatonin significantly reduces the level of aldehyde and ketone protein derivatives, restores glycated haemoglobin level and white blood cell count., (© The Author 2017. Medical Council on Alcohol and Oxford University Press. All rights reserved.)