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Microplastics (MPs) have attracted significant attention due to their global distribution in living environments. Although some studies have reported MP-induced hepatotoxicity in mouse models, a systematic approach to MP-mediated liver toxicity was still lacking. Therefore, we used a mouse model to study the sub-chronic effects of MP exposure on the liver. Female C57BL/6 mice, aged 6 weeks, received an oral administration of 0.3 mg of Nile Red-labeled polystyrene (PS) microplastics, with particle sizes of 0.5 µm (submicron) and 5 µm (micron), via gavage, while control mice received vehicle only. Each mouse was exposed to MPs twice a week for 12 weeks. After sacrifice, the levels of MP accumulation, oxidative stress, inflammation, and pathological changes were measured in the mouse liver, and blood samples were collected for serum biochemistry analysis. Our results demonstrated that 0.5 µm PS-MPs were accumulated in mouse livers post-MP exposure, but not in the 5 µm MP exposure group. Simultaneously, increased levels of glucose, triglyceride, alanine transaminase (ALT), aspartate transaminase (AST), superoxide dismutase, 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA), interleukin-6, and lipid droplets were found in the 0.5 µm MP exposure group, while the fewer responses, including elevated liver weight index, glucose, high-density lipoprotein, AST, and decreased HNE-MA were observed in 5 µm MP exposure group. These results indicate that sub-chronic exposure to submicron MPs causes MP deposition in mouse livers, which further induces oxidative stress, increases inflammatory cytokines and perturbs glucose and lipid homeostasis, which might trigger more severe metabolic dysfunction or non-alcoholic steatohepatitis-like hepatotoxicity., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Liquid smoke products are widely used as a food additive to create a desired smoke flavour. These products may contain hazardous chemicals generated during the wood-burning process. However, the toxic effects of these types of hazardous chemicals constituting in the commercially available products are largely unknown. Therefore, a test battery of cell-based in vitro methods, covering different modes of actions of high relevance to human health, was applied to study liquid smoke products. Ten liquid smoke flavourings were tested as non-extracted and extracted. To assess the potential drivers of toxicity, we used two different solvents. The battery of in vitro methods covered estrogenicity, androgenicity, oxidative stress, aryl hydrocarbon receptor activity and genotoxicity. The non-extracted samples were tested at concentrations 0.002 to 1 μL liquid smoke flavouring/mL culture medium, while extracted samples were tested from 0.003 to 200 μL/mL. Genotoxicity was observed for nearly all non-extracted and all hexane-extracted samples, in which the former had higher potency. No genotoxicity was observed for ethyl acetate-extracted samples. Oxidative stress was activated by almost all extracted and non-extracted samples, while approximately half of the samples had aryl hydrocarbon receptor and estrogen receptor activities. This study used effect-based methods to evaluate the complex mixtures of liquid smoke flavourings. The increased bioactivities seen upon extractions indicate that non-polar chemicals are driving the genotoxicity, while polar substances are increasing oxidative stress and cytotoxic responses. The differences in responses indicate that non-extracted products contain chemicals that are able to antagonize toxic effects, and upon extraction, the protective substances are lost., (© 2021. The Author(s).)

The use of metal oxide nanoparticles (NPs) in skincare products has significantly increased human skin exposure, raising safety concerns. Whilst NP's ability to penetrate healthy skin is minimal, studies have demonstrated that metal oxide NPs can induce toxicity in keratinocytes through direct contact. Moreover, NP's effect on common skin disorders like psoriasis, where barrier impairments and underlying inflammation could potentially increase NP penetration and worsen nanotoxicity is largely unstudied. In this paper, we investigated whether psoriasis-like human keratinocytes (Pso HKs) would exhibit heightened toxic responses to titanium dioxide (TiO 2 ), zinc oxide (ZnO), and/or silica (SiO 2 ) NPs compared to healthy HKs. Cells were exposed to each NP at concentrations ranging between 0.5 and 500 µg/ml for 6, 24, and 48 h. Amongst the metal oxide NPs, ZnO NPs produced the most pronounced toxic effects in both cell types, affecting cell viability, inducing oxidative stress, and activating the inflammasome pathway. Notably, only in ZnO NPs-treated Pso HKs, trappin-2/pre-elafin was cleaved intracellularly through a non-canonical process. In addition, tissue remodelling-related cytokines were upregulated in ZnO NP-treated Pso HKs. The full impact of the observed outcomes on psoriatic symptoms will need further evaluation. Nonetheless, our findings indicate the importance of understanding the sub-lethal impacts of NP exposures on keratinocytes, even though direct exposure may be low, particularly in the context of skin disorders where repeated and long-term exposures are anticipated., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Protein oxidation is a topic of indisputable scientific interest given the impact of oxidized proteins on food quality and safety. Carbonylation is regarded as one of the most notable post-translational modifications in proteins and yet, this reaction and its consequences are poorly understood. From a mechanistic perspective, primary protein carbonyls (i.e. α-aminoadipic and γ-glutamic semialdehydes) have been linked to radical-mediated oxidative stress, but recent studies emphasize the role alternative carbonylation pathways linked to the Maillard reaction. Secondary protein carbonyls are introduced in proteins via covalent linkage of lipid carbonyls (i.e. protein-bound malondialdehyde). The high reactivity of protein carbonyls in foods and other biological systems indicates the intricate chemistry of these species and urges further research to provide insight into these molecular mechanisms and pathways. In particular, protein carbonyls are involved in the formation of aberrant and dysfunctional protein aggregates, undergo further oxidation to yield carboxylic acids of biological relevance and establish interactions with other biomolecules such as oxidizing lipids and phytochemicals. From a methodological perspective, the routine dinitrophenylhydrazine (DNPH) method is criticized not only for the lack of accuracy and consistency but also authors typically perform a poor interpretation of DNPH results, which leads to misleading conclusions. From a practical perspective, the biological relevance of protein carbonyls in the field of food science and nutrition is still a topic of debate. Though the implication of carbonylation on impaired protein functionality and poor protein digestibility is generally recognized, the underlying mechanism of such connections requires further clarification. From a medical perspective, protein carbonyls are highlighted as markers of protein oxidation, oxidative stress and disease. Yet, the specific role of specific protein carbonyls in the onset of particular biological impairments needs further investigations. Recent studies indicates that regardless of the origin (in vivo or dietary) protein carbonyls may act as signalling molecules which activate not only the endogenous antioxidant defences but also implicate the immune system. The present paper concisely reviews the most recent advances in this topic to identify, when applicable, potential fields of interest for future studies., (© 2021. The Author(s).)

Oxidative stress is a pathological process related to not only animal kingdom but also plants. Regarding oxidative stress in plants, heavy metals are frequently discussed as causative stimuli with relevance to ecology. Because heavy metals have broad technological importance, they can easily contaminate the environment. Much of previous effort regarding the harmful impact of the heavy metals was given to their toxicology in the animals and humans. Their implication in plant pathogeneses is less known and remains underestimated.The current paper summarizes basic facts about heavy metals, their distribution in soil, mobility, accumulation by plants, and initiation of oxidative stress including the decline in basal metabolism. The both actual and frontier studies in the field are summarized and discussed. The major pathophysiological pathways are introduced as well and link between heavy metals toxicity and their ability to initiate an oxidative damage is provided. Mobility and bioaccessibility of the metals is also considered as key factors in their impact on oxidative stress development in the plant. The metals like lead, mercury, copper, cadmium, iron, zinc, nickel, vanadium are depicted in the text.Heavy metals appear to be significant contributors to pathological processes in the plants and oxidative stress is probably an important contributor to the effect. The most sensitive plant species are enlisted and discussed in this review. The facts presented here outline next effort to investigate pathological processes in the plants.

Extremely low frequency magnetic fields (ELF-MF) have been classified as "possibly carcinogenic", but their genotoxic effects are still unclear. Recent findings indicate that epigenetic mechanisms contribute to the genome dysfunction and it is well known that they are affected by environmental factors. To our knowledge, to date the question of whether exposure to ELF-MF can influence epigenetic modifications has been poorly addressed. In this paper, we investigated whether exposure to ELF-MF alone and in combination with oxidative stress (OS) can affect DNA methylation, which is one of the most often studied epigenetic modification. To this end, we analyzed the DNA methylation levels of the 5'untranslated region (5'UTR) of long interspersed nuclear element-1s (LINE-1 or L1), which are commonly used to evaluate the global genome methylation level. Human neural cells (BE(2)C) were exposed for 24 and 48 h to extremely low frequency pulsed magnetic field (PMF; 50 Hz, 1 mT) in combination with OS. The methylation levels of CpGs located in L1 5'UTR region were measured by MassARRAY EpiTYPER. The results indicate that exposures to the single agents PMF and OS induced weak decreases and increases of DNA methylation levels at different CpGs. However, the combined exposure to PMF and OS lead to significant decrease of DNA methylation levels at different CpG sites. Most of the changes were transient, suggesting that cells can restore homeostatic DNA methylation patterns. The results are discussed and future research directions outlined.

Background: Kaurenoic acid (KA), a diterpene extracted from copaíba oil-resin, is known to have potent antioxidant and anti-inflammatory properties. L-Arginine (LA) is an amino acid and a nitrogenous precursor for the synthesis of nitric oxide (NO). NO paper in wound healing has already been well documented. The aim of this study was to investigate the protective effects of LA and KA against ischemia reperfusion injury in a randomized skin flap model in rats., Methods: A modified McFarlane flap model measuring 2.5 wide × 8 cm long was established in 36 anesthetized rats and evaluated within 3 groups: group control, group L-arginine, and group kaurenoic acid. Each group was subdivided into two subgroups (T1 and T2, n = 6 each). Samples were collected 24 h (T1)/48 h (T2) postoperatively for oxidative stress (glutathione), as non-protein thiols, malondialdehyde (MDA), NO2, inflammation [myeloperoxidase (MPO)], and cytokines TNF-α and IL-1β assays., Results: KA promoted a significant decrease of TNF-α and IL-1 expression and MPO activity at T1/T2 time points. NSGH levels increased significantly in KA-treated rats, while MDA levels decreased significantly in the same rats. Arginine promoted a significant decrease in MDA levels at the T1 time point and a significant increase in non-protein thiols concentrations at T1/T2 time points. NO2 concentration also decreased at the T1 time point., Conclusions: KA may attenuate the oxidative stress and the inflammation, thereby reducing tissue damage induced by ischemia/reperfusion in rats subjected to dorsal skin flaps., No Level Assigned: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://www.springer.com/00266.

The purpose of this study was to determine the effects of supra-physiological doses of testosterone (TES) on membrane oxidation of activated human neutrophils in vitro using an innovative and sensitive technique: the real-time detection with the fluorescence probe C11-BODIPY(581/591). Methodological controls were performed with the lipid-soluble and powerful antioxidant astaxanthin at different neutrophil density cultures. Neutrophils from nine healthy young men (23.4 ± 2.5 years, 174.4 ± 7.0 cm height, and 78.3 ± 7.0 kg weight) were isolated and treated with 0.1 or 10 μM TES for 24 h and subsequently labeled with the free radical-sensitive probe C11-BODIPY(581/591) for monitoring membrane oxidation after neutrophil activation with phorbol-12-myristate-13-acetate (PMA). First-order exponential decay kinetic indicated that both 0.1 and 10 μM TES severely increased baseline membrane oxidation in non-activated human neutrophils (compared to control). However, similar kinetics of membrane oxidation were observed in control and 0.1 μM TES-treated neutrophils after PMA activation, whereas chemical activation did not alter the baseline higher rates of membrane oxidation in 10 μM TES-treated neutrophils. The data presented here support the hypothesis that TES exerts distinct effects on the membrane oxidation of human neutrophils, depending on its dose (here, 10(2) to 10(4)-fold higher than physiological levels in men) and on PMA activation of the oxidative burst. Furthermore, this paper also presents an innovative application of the free radical-sensitive probe C11-BODIPY(581/591) for monitoring (auto-induced) membrane oxidation as an important parameter of viability and, thus, responsiveness of immune cells in inflammatory processes.

Parkinson's disease (PD) is a neurodegenerative movement disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra and depletion of dopamine in the striatum, which lead to pathological and clinical abnormalities. Increasing evidence has demonstrated that inflammation is the fundamental process contributing to neuron death in PD. Neuroinflammation, which is characterized by activated microglia and infiltrating T cells at sites of neuronal injury, is a prominent contributor to the pathogenesis of progressive PD. Microglia play a critical role in forming a self-propelling cycle leading to sustained chronic neuroinflammation and driving the progressive neurodegeneration in PD. This activation depends heavily on the respiratory burst within the microglia, which in turn regulates a number of downstream pro-inflammatory activities. On the other hand, the adaptive immune responses, most notably T cells, are now emerging as important components of the inflammatory response that contribute to the pathogenesis of PD. This review paper focus on the understanding of the inflammatory etiology of PD, as well as the molecular signaling involved in this inflammatory response, with the aim to provide more effective treatments to slow down or halt the progression of chronic inflammation-induced CNS disorders, such as PD.

In Parkinson's disease, impaired function of mitochondrial complex I is involved in selective degeneration of dopamine neurons in the substantia nigra. Mitochondria are now considered to play an active role in neuronal death process through activating "intrinsic" apoptotic signaling, in addition to production of reactive oxygen species. This paper presents our recent findings on new functions of mitochondria in regulation of their redox state and function through reversible "S-glutathionylation", a mixed disulfide binding between sulfhydryl groups of GSH and protein cysteine in complex I subunits. Type A monoamine oxidase (MAO-A) localized at the mitochondrial outer membrane is a binding site of neurotoxins leading to apoptosis. Rasagiline and (-)deprenyl, type B MAO inhibitors of propagylamine-derivatives, bind to MAO-A to protect neuronal cells against apoptosis through induction of pro-survival Bcl-2 and neurotrophic factors. This review discusses the new role of mitochondria in regulation of neuronal cell death of neurodegenerative disorders.

Increased risk of hypertension after methylmercury (MeHg) exposure has been suggested. However, the underlying mechanisms are not well explored. In this paper, we have analyzed whether sub-chronic exposure to MeHg increases systolic blood pressure even at very low levels. In addition, we analyzed if the methylmercury-induced hypertension is associated with a decreased plasmatic nitric oxide levels and with a dysregulation of the activities of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), as well as the levels of MDA and glutathione. For this study, Wistar rats were treated with methylmercury chloride (100 microg/kg per day) or vehicle. Total treatment time was 100 days. Malondialdehyde (MDA) and circulating NOx levels and superoxide dismutase (SOD) and catalase (CAT) activities were determined in plasma, whereas glutathione levels were determined in erythrocytes. Our results show that long-term treatment at a low level of MeHg affected systolic blood pressure, increasing and reducing the levels of plasmatic MDA and NOx, respectively. However, the activity of SOD did not decrease in the MeHg exposed group when compared to the control. We found a negative correlation between plasmatic nitrite/nitrate (NOx) levels and systolic blood pressure (r = -0.67; P = 0.001), and a positive correlation between MDA and systolic blood pressure (r = 0.61; P = 0.03), thus suggesting increased inhibition of NO formation with the increase of hypertension. In conclusion, long-term exposure to a low dose of MeHg increases the systolic pressure and is associated, at least in part, with increased production of ROS as judged by increased production of malondialdehyde and depressed NO availability.

Acute, short term cooling of North Sea eelpout Zoarces viviparus is associated with a reduction of tissue redox state and activation of hypoxia inducible factor (HIF-1) in the liver. The present study explores the response of HIF-1 to seasonal cold in Zoarces viviparus, and to latitudinal cold by comparing the eurythermal North Sea fish to stenothermal Antarctic eelpout (Pachycara brachycephalum). Hypoxic signalling (HIF-1 DNA binding activity) was studied in liver of summer and winter North Sea eelpout as well as of Antarctic eelpout at habitat temperature of 0 degrees C and after long-term warming to 5 degrees C. Biochemical parameters like tissue iron content, glutathione redox ratio, and oxidative stress indicators were analyzed to see whether the cellular redox state or reactive oxygen species formation and HIF activation in the fish correlate. HIF-1 DNA binding activity was significantly higher at cold temperature, both in the interspecific comparison, polar vs. temperate species, and when comparing winter and summer North Sea eelpout. Compared at the low acclimation temperatures (0 degrees C for the polar and 6 degrees C for the temperate eelpout) the polar fish showed lower levels of lipid peroxidation although the liver microsomal fraction turned out to be more susceptible to lipid radical formation. The level of radical scavenger, glutathione, was twofold higher in polar than in North Sea eelpout and also oxidised to over 50%. Under both conditions of cold exposure, latitudinal cold in the Antarctic and seasonal cold in the North Sea eelpout, the glutathione redox ratio was more oxidised when compared to the warmer condition. However, oxidative damage parameters (protein carbonyls and thiobarbituric acid reactive substances (TBARS) were elevated only during seasonal cold exposure in Z. viviparus. Obviously, Antarctic eelpout are keeping oxidative defence mechanisms high enough to avoid accumulation of oxidative damage products at low habitat temperature. The paper discusses how HIF could be instrumental in cold adaptation in fish.

Oxidative stress induces various post-translational modifications (PTM); some are reversible in vivo via enzymatic catalysis. The present paper reviews specific procedures for the detection of oxidative PTM in proteins, most of them including electrophoresis. Main topics are carbonylated and glutathionylated proteins as well as modification of selected amino acids (Cys, Tyr, Met, Trp, Lys).

Synchrotron FTIR can provide high spatial resolution (<10 microm pixel size) in situ biochemical analyses of intact biotissues, an area of increasing importance in the post-genomic era, as gene functions and gene networks are coming under direct scrutiny. With this technique, we can simultaneously assess multiple aspects of cell biochemistry and cytoplasmic composition. In this paper, we report the first results of our synchrotron FTIR examination of hyphae of three important fungal model systems, each with sequenced genomes and a wealth of research: Aspergillus, Neurospora, and Rhizopus. We have analyzed the FTIR maps of Aspergillus nidulans cells containing the hypA1 allele, a well-characterized single-gene temperature-sensitive morphogenetic mutation. The hypA1 cells resemble wildtype at 28 degrees C but have growth defects at 42 degrees C. We have also investigated Neurospora and Rhizopus cultures grown in media with optimal or elevated pH. Significant differences between the spectra of the three fungi are likely related to differences in composition and structure. In addition, high spatial resolution synchrotron FTIR spectroscopy provides an outstanding method for monitoring subtle subcellular changes that accompany environmental stress.

Parkinson's disease is characterized by the selective depletion of dopamine neurons in the substantia nigra, particular those containing neuromelanin. Involvement of neuromelanin in the pathogenesis may be either cytotoxic or protective. Recently we found that neuromelanin reduces the activity of 26S proteasome. In this paper, the detailed mechanisms behind the reduced activity were studied using neuromelanin isolated from the human brain. Neuromelanin increased the oxidative stress, but synthetic melanin did not. Superoxide dismutase and deferoxamine completely suppressed the increase, indicating that superoxide produced by an iron-mediated reaction plays a central role. Iron was shown to reduce in situ 26S proteasome activity in SH-SY5Y cells and the reduction was protected by antioxidants. These results suggest that iron released from neuromelanin increases oxidative stress in mitochondria, and then causes mitochondrial dysfunction and reduces proteasome function. The role of neuromelanin is discussed in relation to the selective vulnerability of dopamine neurons in Parkinson's disease.

In Alzheimer's disease amyloid beta peptide (Abeta) produced from amyloid precursor protein (APP) is considered to induce cell death. To clarify the molecular mechanism underlying Abeta neurotoxicity, we established the cell line overexpressing wild or mutant (His684Arg) APP in human SH-SY5Y cells. This paper presents that overexpression of wild-APP in the cells (SH/w-APP) increased the levels of APP and Abeta(1-40) but not Abeta(1-42), and reduced Bcl-2 level and proteasome activity with increased susceptibility to oxidative stress. The intracellular levels of reactive oxygen species in SH/w-APP increased significantly by H(2)O(2) treatment. The level of Bcl-2 protein, but not mRNA, was markedly decreased in SH/w-APP cells, which was inversely correlated with APP expression among subcloned SH/w-APP cells. These results indicate that increased expression of wild type APP renders neuronal cells more vulnerable to oxidative stress leading to cell death.

The SoxRS regulon is induced when bacterial cells are exposed to redox-cycling agents such as menadione or paraquat. In this paper it is shown that a physical agent, such as ultraviolet radiation with a wavelength of 312 nm (UVB) can induce soxS gene expression. The results indicate that this induction involves the RpoS protein. Moreover, an unexpected increase of soxS gene expression independent of a functional soxR gene in UVB-irradiated cells has been verified. This increase could be explained by transcription of soxS gene in a rpoS-dependent pathway.

Nodularin is a hepatotoxin from a cyanobacterium, Nodularia spumigena, that inhibits protein phosphatases 1 and 2 and posseses tumor-promoting activity. The aim of this paper was to examine whether nodularin is able to induce oxidative stress in mouse liver tissue and whether melatonin (protective compound against oxidative damage) could supress the activity of nodularin. We studied the effect of nodularin (1, 5, and 10 microg/kg body weight) and melatonin (5, 10, and 15 mg/kg body weight) administration on the activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) in mouse liver. Intraperitoneal treatment of mice with nodularin per 7 days decreased the activities of all estimated enzymes in a dose-dependent manner. Intraperitoneal treatment of animals with melatonin per 7 days increased the activities of SOD, CAT, and GSH-Px and this effect was concentration-dependent. Co-treatment (nodularin 5 microg/kg body weight + melatonin 5, 10, and 15 mg/kg body weight per 7 days) and post-treatment with melatonin (nodularin 5 microg/kg body weight per 7 days + melatonin 5, 10, and 15 mg/kg body weight per next 7 days) increased the activities of SOD, CAT, and GSH-Px in comparison to the nodularin group. No significant differences from the nodularin group were noted in the group after pre-treatment with melatonin. In conclusion, these findings suggest that oxidative damage may be involved in the toxicity of nodularin. Moreover, co-treatment and post-treatment with 10 and 15 mg/kg body weight of melatonin may protect against nodularin-induced oxidative stress. There was no protective effect of pre-treatment with melatonin.