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Since even low-level environmental exposure to cadmium (Cd) can lead to numerous unfavourable health outcomes, including damage to the nervous system, it is important to recognize the risk of health damage by this xenobiotic, the mechanisms of its toxic influence, and to find an effective protective strategy. This study aimed to evaluate, in a female Wistar rat model of current human environmental exposure to Cd (1 and 5 mg/kg of diet for 3-24 months), if the low-to-moderate treatment with this element can harm the brain and whether the supplementation with a 0.1% Aronia melanocarpa L. (Michx.) Elliott berries (chokeberries) extract (AE) can protect against this effect. The exposure to Cd modified the values of various biomarkers of neurotoxicity, including enzymes (acetylcholinesterase (AChE), sodium-potassium adenosine triphosphatase (Na + /K + -ATPase), phospholipase A2 (PLA2), and nitric oxide synthase 1 (NOS1)) and non-enzymatic proteins (calmodulin (CAM), nuclear factor erythroid 2-related factor 2 (Nrf2), and Kelch-like ECH-associated protein 1 (KEAP1)) crucial for the functioning of the nervous system, as well as the concentrations of calcium (Ca) and magnesium (Mg) and some metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in the brain tissue. The co-administration of AE, partially or entirely, protected from most of the Cd-induced changes alleviating its neurotoxic influence. In conclusion, even low-level chronic exposure to Cd may adversely affect the nervous system, whereas the supplementation with A. melanocarpa berries products during the treatment seems a protective strategy.

Cadmium (Cd) is a prooxidant that adversely affects human health, including the nervous system. As exposure of the general population to this heavy metal is inevitable, it is crucial to look for agents that can prevent the effects of its toxic action. An experimental model on female rats of current lifetime human exposure to cadmium (3-24-months' treatment with 1 or 5 mg Cd/kg diet) was used to test whether low-level and moderate intoxication can exert a prooxidative impact in the brain and whether supplementation with a 0.1% extract from the berries of Aronia melanocarpa L. (Michx.) Elliott (AE; chokeberry extract) can protect against this action. Numerous parameters of the non-enzymatic and enzymatic antioxidative barrier, as well as total antioxidative and oxidative status (TAS and TOS, respectively), were determined and the index of oxidative stress (OSI) was calculated. Moreover, chosen prooxidants (myeloperoxidase, xanthine oxidase, and hydrogen peroxide) and biomarkers of oxidative modifications of lipids, proteins, and deoxyribonucleic acid were assayed. Cadmium dysregulated the balance between oxidants and antioxidants in the brain and led to oxidative stress and oxidative injury of the cellular macromolecules, whereas the co-administration of AE alleviated these effects. To summarize, long-term, even low-level, cadmium exposure can pose a risk of failure of the nervous system by the induction of oxidative stress in the brain, whereas supplementation with products based on aronia berries seems to be an effective protective strategy., Competing Interests: The authors declare no conflicts of interest.

The impact of cadmium (Cd) on the function and structure of the kidney and the potential protective effect of an extract from Aronia melanocarpa L. berries were investigated in a rat model of low- and moderate-level environmental exposure to this heavy metal (1 and 5 mg Cd/kg feed for up to 24 months). The sensitive biomarkers of Cd-induced damage to the kidney tubules (N-acetyl-β-D-glucosaminidase (NAG), alkaline phosphatase (ALP), β2-microglobulin (β2-MG), and kidney injury molecule-1 (KIM-1) in the urine), clinically relevant early markers of glomerular damage (albumin in the urine and creatinine clearance), and other markers of the general functional status of this organ (urea, uric acid, and total protein in the serum and/or urine) and Cd concentration in the urine, were evaluated. The morphological structure of the kidney and inflammatory markers (chemerin, macrophage inflammatory protein 1 alpha (MIP1a), and Bcl2-associated X protein (Bax)) were also estimated. Low-level and moderate exposure to Cd led to damage to the function and structure of the kidney tubules and glomeruli. The co-administration of A. melanocarpa berry extract significantly protected against the injurious impact of this toxic element. In conclusion, even low-level, long-term exposure to Cd poses a risk of kidney damage, whereas an intake of Aronia berry products may effectively protect from this outcome.

The growing number of reports indicating unfavorable outcomes for human health upon environmental exposure to cadmium (Cd) have focused attention on the threat to the general population posed by this heavy metal. The kidney is a target organ during chronic Cd intoxication. The aim of this article was to critically review the available literature on the impact of the current levels of environmental exposure to this xenobiotic in industrialized countries on the kidney, and to evaluate the associated risk of organ damage, including chronic kidney disease (CKD). Based on a comprehensive review of the available data, we recognized that the observed adverse effect levels (NOAELs) of Cd concentration in the blood and urine for clinically relevant kidney damage (glomerular dysfunction) are 0.18 μg/L and 0.27 μg/g creatinine, respectively, whereas the lowest observed adverse effect levels (LOAELs) are >0.18 μg/L and >0.27 μg/g creatinine, respectively, which are within the lower range of concentrations noted in inhabitants of industrialized countries. In conclusion, the current levels of environmental exposure to Cd may increase the risk of clinically relevant kidney damage, resulting in, or at least contributing to, the development of CKD.

Obstructive sleep apnea (OSA) is a prevalent, underdiagnosed disease and is considered a risk factor for cardiovascular diseases, depression, accidents, and stroke. Recent clinical practice guidelines for OSA expressed the need for a new clinical tool that establishes the Apnea-Hypopnea Index (AHI) to determine the disease burden. The serum and plasma concentrations of Osteoprotegerin (OPG), Chitinase 3-like protein 1 (YKL-40), and Cardiotrophin-1 (CT-1) in 80 subjects-52 OSA patients, 27 moderate (15 ≤ AHI ˂ 30) and 25 severe (AHI ≥ 30), and 28 non-OSA controls (AHI 0-5)-were determined. Moreover, the Total Oxidative Status (TOS), Total Antioxidative Status (TAS), and Oxidative Stress Index (OSI) were assessed in the serum and plasma to evaluate whether the severity of OSA and the concentrations of OPG, YKL-40, and CT-1 correlate with the oxidative/reductive status. The serum and plasma concentrations of YKL-40 and CT-1 were higher in the OSA group, whereas the serum and plasma concentrations of OPG were lower compared to the control group. The concentrations of OPG, YKL-40, and CT-1 in the serum and plasma correlated with AHI; however, a better correlation of the concentrations was obtained for the above-mentioned proteins in the plasma. The concentrations of YKL-40 and CT-1 in the serum and OPG in the plasma show better diagnostic capabilities for moderate and severe OSA than the concentrations of YKL-40 and CT-1 in the plasma and the concentrations of OPG in the serum.

Nowadays, more and more attention has been focused on the risk of the neurotoxic action of cadmium (Cd) under environmental exposure. Due to the growing incidence of nervous system diseases, including neurodegenerative changes, and suggested involvement of Cd in their aetiopathogenesis, this review aimed to discuss critically this element neurotoxicity. Attempts have been made to recognize at which concentrations in the blood and urine Cd may increase the risk of damage to the nervous system and compare it to the risk of injury of other organs and systems. The performed overview of the available literature shows that Cd may have an unfavourable impact on the human's nervous system at the concentration >0.8 μg Cd/L in the urine and >0.6 μg Cd/L in the blood. Because such concentrations are currently noted in the general population of industrialized countries, it can be concluded that environmental exposure to this xenobiotic may create a risk of damage to the nervous system and be involved in the aetiopathogenesis of neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, as well as worsening cognitive and behavioural functions. The potential mechanism of Cd neurotoxicity consists in inducing oxidative stress, disrupting the activity of enzymes essential to the proper functioning of the nervous system and destroying the homoeostasis of bioelements in the brain. Thus, further studies are necessary to recognize accurately both the risk of nervous system damage in the general population due to environmental exposure to Cd and the mechanism of this action., (© 2022 The Authors. Journal of Applied Toxicology published by John Wiley & Sons Ltd.)

The impact of a polyphenol-rich 0.1% aqueous extract from Aronia melanocarpa L. berries (AE) on the body status of manganese (Mn) and the activity of this essential element-dependent mitochondrial superoxide dismutase (MnSOD) during treatment with cadmium (Cd) was investigated in a rat model of low-level and moderate environmental human exposure to this xenobiotic (1 and 5 mg Cd/kg diet, respectively, for 3-24 months). The exposure to Cd, dose- and duration-dependently, affected the body status of Mn (apparent absorption, body retention, serum and tissue concentrations, content in some organs and total Mn body burden, and urinary and faecal excretion) and the activity of MnSOD in the mitochondria of the liver, kidney, and brain. The administration of AE during the exposure to Cd prevented or at least partially protected the animals from the perturbation of the metabolism of Mn, as well as ameliorated changes in the activity of MnSOD and the concentration of Mn and protected from Cd accumulation in the mitochondria. In conclusion, AE may protect from disorders in the body status of Mn and influence the antioxidative capacity of cells under chronic exposure to Cd. The findings confirm the protective impact of aronia berries products against Cd toxicity.

In an in vivo rat model of human exposure to cadmium (Cd; 5 and 50 mg/L, 6 months), whether the supplementation with zinc (Zn; 30 and 60 mg/L, increasing its daily intake by 79% and 151%, respectively) protects against the unfavourable impact of this xenobiotic on the vascular tissue of the abdominal aorta was investigated. The treatment with Cd led to oxidative stress and increased the concentrations of pro-inflammatory interleukin 1β (IL-1β), total cholesterol (TC), triglycerides (TG), and endothelial nitric oxide synthase (eNOS) and decreased the concentration of anti-inflammatory interleukin 10 (IL-10) in the vascular tissue. Cd decreased the expression of intercellular adhesion molecule-1 (ICAM-1), platelet endothelial cell adhesion molecule-1 (PECAM-1), and L-selectin on the endothelial cells. The administration of Zn prevented most of the Cd-induced alterations or at least weakened them (except for the expression of adhesive molecules). In conclusion, Zn supplementation may protect from the toxic impact of Cd on the blood vessels and thus exert a beneficial influence on the cardiovascular system. The increase in the intake of Zn by 79% may be sufficient to provide this protection and the effect is related to the antioxidative, anti-inflammatory, and antiatherogenic properties of this essential element., Competing Interests: The authors declare no conflict of interest.

Cadmium (Cd) is one of the most harmful xenobiotics to which humans are exposed, mainly by the oral route, throughout life. Preventive strategies are searched as low intoxication with this element, among others due to its prooxidative properties, can be deleterious to health and the exposure to it is continuously increasing. Recently, interest has been paid to plant raw materials with a high antioxidative potential to oppose the prooxidative properties of cadmium, such as black chokeberry ( Aronia melanocarpa L. fruit), which is rich in polyphenolic compounds. The study was aimed at assessing whether the chokeberry extract may counteract the prooxidative impact of low-level and moderate repeated intoxication with cadmium on the sublingual salivary gland. The investigation was performed on 96 Wistar rats (females), which were treated with a 0.1% aqueous extract from chokeberries or/and a diet containing 1 or 5 mg Cd/kg for 3 and 10 months, and control animals. The intoxication with cadmium, in a dose- and time-dependent manner, attenuated the enzymatic and nonenzymatic antioxidative potential and increased the concentration of hydrogen peroxide and total oxidative status of the sublingual salivary gland resulting in an occurrence of oxidative stress, enhancement of lipid peroxidation, and oxidative injuries of proteins in this salivary gland. The treatment with the black chokeberry extract during the intoxication with cadmium prevented this xenobiotic-caused oxidative/reductive imbalance and oxidative modifications of proteins and lipids in the salivary gland. The above results allow the conclusion that the consumption of black chokeberry products during intoxication with cadmium can prevent oxidative stress and its consequences in the sublingual salivary gland and thus counteract the unfavourable impact of this xenobiotic on the oral cavity., Competing Interests: There is no conflict of interest., (Copyright © 2021 Barbara M. Onopiuk et al.)

UVA/UVB radiation disturbs the redox balance of skin cells, and metabolic consequences can be transferred into the blood and internal tissues, especially after chronic skin exposure to UV radiation. Therefore, the aim of this study was to evaluate the effect of cannabidiol (CBD), an antioxidant and anti-inflammatory phytocannabinoid, on oxidative stress and its consequences in the blood of nude rats whose skin was exposed to UVA/UVB radiation for 4 weeks. It was shown that CBD penetrated the blood and in UVB-irradiated rats was preferentially located in the membranes of polymorphonuclear leukocytes, which promoted reduction of ROS generation and up-regulation of antioxidant ability by increasing the activity of glutathione reductase and thioredoxin reductase, while the level of reduced glutathione decreased by UV radiation. Consequently, reduction in UV-induced lipid peroxidation, assessed as 4-hydroxynonenal (4-HNE) and 8-isoprostane (8-isoPGF2α) as well as protein modifications, estimated as 4-HNE-protein adducts and protein carbonyl groups, was observed. CBD, by countering the UV-induced down-regulation of 2-arachidonylglycerol, promoted its antioxidant/anti-inflammatory effects by reducing CB1 and increasing PPARγ receptor activation and consequently ROS and TNF-α down-regulation. The results suggest that CBD applied topically to the skin minimizes redox changes not only at the skin level, but also at the systemic level.

The hypothesis that individuals with obstructive sleep apnea syndrome (OSAS) demonstrate oxidative stress in the uvular mucosa that correlates with OSAS occurrence was investigated. A total of 128 participants (mean age 45.8, mean body mass index 30.7, female-male ratio 1:20) were divided into the non-OSAS group (apnea-hypopnea index-AHI < 5) and OSAS-group (AHI ≥ 5), in which mild (5 ≤ AHI < 15), moderate (15 ≤ AHI < 30), and severe (AHI ≥ 30) sub-groups were distinguished. Laryngological examination, Epworth Sleep Scale questionnaire, and home sleep study were performed to obtain AHI, mean oxygen saturation, and lowest oxygen saturation. Total oxidative status (TOS) and total antioxidative status (TAS) were assayed in the uvular mucosa taken during palatoplasty or palatopharyngoplasty. The severity of oxidative stress was expressed as oxidative stress index (OSI). Oxidative/reductive imbalance was noted in the mucosa of the uvula of OSAS individuals, and TAS of the uvular mucosa negatively correlated with the severity of this syndrome. TOS and OSI in the mild, moderate, and severe OSAS were higher than in the non-OSAS group, whereas TAS of the uvular mucosa in the OSAS group was lower compared to the non-OSAS group. In conclusion, oxidative stress in the uvular mucosa is associated with the occurrence of OSAS.

We examined, in a rat model of moderate environmental human exposure to cadmium (Cd), whether the enhanced intake of zinc (Zn) may protect against Cd-caused destroying the oxidative/antioxidative balance and its consequences in the brain. The intoxication with Cd (5 mg/L, 6 months) weakened the enzymatic (superoxide dismutase, glutathione peroxidase, catalase) and non-enzymatic (total thiol groups, reduced glutathione) antioxidative barrier decreasing the total antioxidative status and increased the concentrations of pro-oxidants (hydrogen peroxide, myeloperoxidase) in this organ and its total oxidative status. These resulted in the development of oxidative stress and oxidative modifications of lipids and proteins. The co-administration of Zn (30 and 60 mg/L enhancing this element intake by 79% and 151%, respectively) importantly protected against Cd accumulation in the brain tissue and this xenobiotic-induced development of oxidative stress and oxidative damage to lipids and proteins. Moreover, this bioelement also prevented Cd-mediated oxidative stress evaluated in the serum. The favorable effect of Zn was caused by its independent action and interaction with Cd. Concluding, the enhancement of Zn intake under oral exposure to Cd may prevent the oxidative/antioxidative imbalance and oxidative stress in the brain and thus protect against injury of cellular macromolecules in the nervous system.

This study examined whether a polyphenol-rich extract from the berries of Aronia melanocarpa L. (AE; chokeberries) may protect from the impact of cadmium (Cd) on the metabolism of collagen in the liver. The study was conducted in an experimental model (rats that were fed a diet containing 1 or 5 mg Cd/kg for 3-24 months) of human exposure to this xenobiotic during a lifetime. The concentration of total collagen and the expression of collagen types I and III at the mRNA and protein levels, as well as the concentrations of matrix metalloproteinases (MMP-1 and MMP-2) and their tissue inhibitors (TIMP-1 and TIMP-2), were assayed. The administration of Cd and/or AE had only a slight and temporary impact on the concentration of total collagen in the liver. The supplementation with AE significantly prevented Cd-mediated changes in the expression of collagen types I and III at the mRNA and protein levels and their ratio (collagen III/collagen I), as well as a rise in the concentrations of MMPs and TIMPs in this organ. The results allow the conclusion that the intake of chokeberry products in the case of Cd intoxication may be effective in prevention from this xenobiotic-induced disturbance in collagen homeostasis in the liver.

Parabens, which are widely used in food, medicines and cosmetics, have a harmful effect on human health. People are most exposed to parabens transdermally by using cosmetic products containing these preservatives. The purpose of this study was to estimate the influence of parabens (methylparaben-MP and propylparaben-PP) on the metabolism of collagen in the human skin fibroblasts and above all, to assess whether rosmarinic acid (RA-50, 100, or 150 M) can protect these cells from the adverse effects of parabens (0.001% MP and 0.0003% PP, 0.003% MP and 0.001% PP, and ​​0.01% MP and 0.003% PP). The possible mechanisms of RA action were estimated as well. Parabens decreased the expression of collagen type I and III at mRNA and protein levels, while RA (depending on the concentration) provided partial or total protection against these changes. The effective protection against the adverse effects of parabens on cell viability and proliferation was also provided by RA. The beneficial impact of RA on collagen and the fibroblasts resulted from an independent action of this compound and its interaction with parabens. This study allows us to conclude that this polyphenolic compound may protect from unfavorable health outcomes caused by lifetime human exposure to parabens contained in cosmetic products., Competing Interests: The authors declare no conflicts of interest.

Previously, we have revealed that prolonged administration of a polyphenol-rich 0.1% extract from the berries of Aronia melanocarpa L. (chokeberries) alone and under chronic exposure to cadmium influences the body status of zinc (Zn) and copper (Cu). The aim of this study was to evaluate, in an in vitro model, the chelating properties of the extract (0.05% and 0.1%) and its main polyphenolic ingredients (cyanidin 3- O - β -galactoside, chlorogenic acid, neochlorogenic acid, (+)-catechin, (-)-epicatechin, quercetin, and kaempferol) regarding divalent ions of Zn (Zn 2+ ) and Cu (Cu 2+ ) at pH reflecting physiological conditions at the gastrointestinal tract such as 2 (empty stomach), 5.5 (full stomach), and 8 (duodenum). The study has revealed that the extract from Aronia berries, as well as cyanidin 3- O - β -galactoside and quercetin, can bind Zn 2+ and Cu 2+ , but only at pH 5.5. Moreover, kaempferol was able to chelate Zn 2+ at pH 5.5; however, this ability was weaker than those of cyanidin 3- O - β -galactoside and quercetin. The ability of the chokeberry extract to chelate Zn 2+ and Cu 2+ may be explained, at least partially, by the presence of polyphenols such as anthocyanin derivatives of cyanidin and quercetin. The findings seem to suggest that Aronia products, used as supplements of a diet, should be consumed before meals, and particular attention should be paid to adequate intake of Zn and Cu under prolonged consumption of these products to avoid deficiency of both bioelements in the body due to their complexation by chokeberry ingredients in the lumen of the gastrointestinal tract.

Oxidative stress underlies the pathomechanisms of toxic action of cadmium (Cd), including its damaging impact on the oral cavity. This study investigated whether the administration of an extract from Aronia melanocarpa L. berries (AME), characterized by their strong antioxidative potential, may have a beneficial impact on the oxidative-reductive status of the submandibular gland in an experimental model of low-level and moderate human environmental exposure to cadmium. The main markers of the antioxidative status (glutathione reductase, superoxide dismutase, catalase, reduced glutathione, total antioxidative status (TAS)), total oxidative status (TOS), oxidative stress index (OSI = TOS/TAS), and lipid peroxides, as well as cadmium concentration, were evaluated in the submandibular gland tissue of female Wistar rats who received a 0.1% aqueous AME and/or a diet containing 0, 1, and 5 mg Cd/kg for 3 and 10 months. The treatment with cadmium decreased the activities of antioxidative enzymes (29%-74%), reduced glutathione concentration (45%-52%), and TAS and increased TOS, resulting in the development of oxidative stress and enhanced concentration of lipid peroxides in the submandibular gland. The administration of AME at both levels of exposure to cadmium offered significant protection against these actions of this xenobiotic. After the 10 month exposure to the 1 and 5 mg Cd/kg diet, TAS was decreased by 77% and 83%, respectively, TOS, OSI, and lipid peroxides concentration were increased by 50% and 52%, respectively, 11.8-fold and 14.4-fold, respectively, and 2.3-fold and 4.3-fold, respectively, whereas, in the case of the extract co-administration, the values of these parameters did not differ compared to the control group. The results indicate that the consumption of aronia products under exposure to cadmium may have a beneficial impact on the oxidative-reductive status of the submandibular gland and prevent oxidative stress development and enhanced lipid peroxidation in this salivary gland., Competing Interests: There is no conflict of interest.

Cosmetics are a source of lifetime exposure to various substances including parabens, being the most popular synthetic preservatives. Because the use of cosmetics shows an increasing trend and some adverse health outcomes of parabens present in these products have been reported, the present review focused on the safety of dermal application of these compounds. Special attention has been paid to the absorption of parabens and their retention in the human body in the intact form, as well as to their toxicological characteristics. Particular emphasis has been placed on the estrogenic potential of parabens. Based on the available published data of the concentrations of parabens in various kinds of cosmetics, the average ranges of systemic exposure dose (SED) for methylparaben, ethylparaben, propylparaben, and butylparaben have been calculated. Safety evaluations [margin of safety (MoS)] for these compounds, based on their aggregate exposure, have also been performed. Moreover, evidence for the negative impact of methylparaben on skin cells has been provided, and the main factors that may intensify dermal absorption of parabens and their impact on the skin have been described. Summarizing, the use of single cosmetics containing parabens should not pose a hazard for human health; however, using excessive quantities of cosmetic preparations containing these compounds may lead to the development of unfavorable health outcomes. Due to the real risk of estrogenic effects, as a result of exposure to parabens in cosmetics, simultaneous use of many cosmetic products containing these preservatives should be avoided., (© 2020 John Wiley & Sons, Ltd.)

It was investigated, using a female rat model of low and moderate exposure of human to cadmium (Cd, 1 and 5 mg Cd/kg diet for 3⁻24 months), whether a polyphenol-rich 0.1% aqueous extract from Aronia melanocarpa L. berries (AE) may prevent Cd-induced lipid peroxidation and oxidative modifications of proteins and deoxyribonucleic acid (DNA) in the liver. For this purpose, markers of lipid peroxidation (lipid peroxides and 8-isoprostane) and oxidative injury of proteins (protein carbonyl groups and 3-nitrotyrosine) and DNA (8-hydroxy-2'-deoxyguanosine) were measured in this organ. The expression of metallothionein 1 (MT1) and metallothionein 2 (MT2) genes was estimated for a better explanation of the possible mechanisms of protective action of AE against Cd hepatotoxicity. The low and moderate treatment with Cd induced lipid peroxidation and oxidatively modified proteins and DNA, as well as enhanced the expression of MT1 and MT2 in the liver, whereas the co-administration of AE completely prevented almost all of these effects. The results allow us to conclude that the consumption of aronia products under exposure to Cd may offer protection against oxidative injury of the main cellular macromolecules in the liver, including especially lipid peroxidation, and in this way prevent damage to this organ.

Recently, the growing attention of the scientific community has been focused on the threat to health created by environmental pollutants, including toxic metals such as cadmium (Cd), and on the need of finding effective ways to prevent and treat the unfavorable health effects of exposure to them. Particularly promising for Cd, and thus arousing the greatest interest, is the possibility of using various ingredients present in plants, including mainly polyphenolic compounds. As the liver is one of the target organs for this toxic metal and disturbances in the proper functioning of this organ have serious consequences for health, the aim of the present review was to discuss the possibility of using polyphenol-rich food products (e.g., chokeberry, black and green tea, blueberry, olive oil, rosemary and ginger) as the strategy in protection from this xenobiotic hepatotoxicity and treatment of this heavy metal-induced liver damage. Owing to the ability of polyphenols to bind ions of Cd and the strong antioxidative potential of these compounds, as well as their abundance in dietary products, it seems to be of high importance to consider the possibility of using polyphenols as potential preventive and therapeutic agents against Cd hepatotoxicity, determined by its strong pro-oxidative properties. Although most of the data on the effectiveness of polyphenols comes from studies in animals, the fact that some of them are derived from experimental models that reflect human exposure to this metal allows us to assume that some polyphenol-rich food products may be promising protective agents against Cd hepatotoxicity in humans., (© 2018 John Wiley & Sons, Ltd.)

The study investigated, in a rat model of low-level and moderate environmental exposure to cadmium (Cd; 1 or 5 mg Cd/kg diet, respectively, for 3 to 24 months), whether the co-administration of 0.1% extract from Aronia melanocarpa L. berries (AE) may protect against oxidative stress in the liver and in this way mediate this organ status. The intoxication with Cd, dose- and duration-dependently, weakened the enzymatic antioxidative barrier, decreased the concentrations of reduced glutathione and total thiol groups, and increased the concentrations of oxidized glutathione, hydrogen peroxide, xanthine oxidase, and myeloperoxidase in this organ. These resulted in a decrease in the total antioxidative status, increase in the total oxidative status and development of oxidative stress (increased oxidative stress index and malondialdehyde concentration) and histopathological changes in the liver. The administration of AE at both levels of Cd treatment significantly improved the enzymatic and nonenzymatic antioxidative barrier, decreased pro-oxidant concentration, and protected from the development of oxidative stress in the liver and changes in its morphology, as well as normalized the serum activities of liver enzymes markers. In conclusion, consumption of aronia products may prevent Cd-induced destroying the oxidative/antioxidative balance and development of oxidative stress in the liver protecting against this organ damage.

Cadmium (Cd) is a toxic metal that damages bone tissue by affecting its mineral and organic components. The organic matrix is mainly (90%) composed of collagen, which determines the biomechanical strength of bone. The aim of this study was to evaluate the effect of zinc (Zn) supplementation (30 or 60 mg l -1 ) under moderate and relatively high exposure to Cd (5 and 50 mg l -1 ) on collagen in the rat tibia proximal epiphysis and diaphysis (regions abundant in trabecular and cortical bone, respectively). Significant decrease in collagen type I biosynthesis was found in both regions of the tibia in Cd-treated rats, whereas the supplementation with Zn provided significant protection against this effect. Western blot confirmed the presence of the major type I collagen in the tibia epiphysis and diaphysis, but collagen type II was revealed only in the epiphysis. Acetic acid- and pepsin-soluble collagen concentration in the tibia epiphysis and diaphysis was significantly increased due to the exposure to Cd, whereas the supplementation with Zn protected, partially or totally, from these effects, depending on the used concentration. The supplementation with Zn also provided protection from unfavorable Cd impact on the maturation of the bone collagen, as the ratio of cross-links to monomers was higher compared to the Cd-treated group. This report confirms our previous findings on the preventive action of Zn against harmful effects of Cd on bone, but additionally, and to the best of our knowledge for the first time, explains the possible mechanism of the beneficial influence of this bioelement., (Copyright © 2018 John Wiley & Sons, Ltd.)

Cadmium (Cd) is a heavy metal belonging to the group of the main chemical pollutants of the natural and occupational environment in economically developed countries. The forecasts indicate that contamination of the environment with this toxic metal, and thus the exposure of the general population, will increase. Food (particularly plant products) is the main source of the general population exposure to this element. Moreover, an important, and often the main, source of intoxication with Cd is habitual tobacco smoking. Recent epidemiological studies have provided numerous evidence that even low-level environmental exposure to this toxic metal, nowadays occurring in numerous economically developed countries, creates a risk for health of the general population. The low-level lifetime exposure to this metal may lead to the damage to the kidneys, liver, skeletal system, and cardiovascular system, as well as to the deterioration of the sight and hearing. Moreover, it has been suggested that environmental exposure to this xenobiotic may contribute to the development of cancer of the lung, breast, prostate, pancreas, urinary bladder, and nasopharynx. Taking the above into account, the aim of this review article is to draw more attention to Cd as an environmental risk factor for the health of the general population and the need to undertake preventive actions allowing to reduce the risk of health damage due to a lifetime exposure to this toxic metal.

In an experimental model of low-level and moderate environmental human exposure to cadmium (Cd), it was investigated whether the consumption of a polyphenol-rich Aronia melanocarpa L. berries (chokeberries) extract (AE) may influence the body status of zinc (Zn) and copper (Cu). The bioelements' apparent absorption, body retention, serum and tissue concentrations, total pool in internal organs, excretion, and the degree of binding to metallothionein were evaluated in female rats administered 0.1% aqueous AE or/and Cd in their diet (1 and 5 mg/kg) for 3-24 months. The consumption of AE alone had no influence on the body status of Zn and Cu. The extract administration at both levels of Cd treatment significantly (completely or partially) protected against most of the changes in the metabolism of Zn and Cu caused by this xenobiotic; however, it increased or decreased some of the Cd-unchanged indices of their body status. Based on the findings, it seems that rational amounts of chokeberry products may be included in the daily diet without the risk of destroying Zn and Cu metabolisms; however, their potential prophylactic use under exposure to Cd needs further study to exclude any unfavourable impact of these essential elements on the metabolism., Competing Interests: The authors declare no conflict of interest.

The hypothesis that the consumption of Aronia melanocarpa berries (chokeberries) extract, recently reported by us to improve bone metabolism in female rats at low-level and moderate chronic exposure to cadmium (1 and 5 mg Cd/kg diet for up to 24 months), may increase the bone resistance to fracture was investigated. Biomechanical properties of the neck (bending test with vertical head loading) and diaphysis (three-point bending test) of the femur of rats administered 0.1% aqueous chokeberry extract (65.74% of polyphenols) or/and Cd in the diet (1 and 5 mg Cd/kg) for 3, 10, 17, and 24 months were evaluated. Moreover, procollagen I was assayed in the bone tissue. The low-level and moderate exposure to Cd decreased the procollagen I concentration in the bone tissue and weakened the biomechanical properties of the femoral neck and diaphysis. Chokeberry extract administration under the exposure to Cd improved the bone collagen biosynthesis and femur biomechanical properties. The results allow for the conclusion that the consumption of chokeberry products under exposure to Cd may improve the bone biomechanical properties and protect from fracture. This study provides support for Aronia melanocarpa berries being a promising natural agent for skeletal protection under low-level and moderate chronic exposure to Cd., Competing Interests: The authors declare no conflict of interest.

Aronia melanocarpa berries (chokeberries) constitute a very rich source of numerous substances exerting a beneficial impact on health, including mainly polyphenols (proanthocyanidins, anthocyanins, flavonoids, and phenolic acids), possessing antioxidative, anti-inflammatory, antiviral, anticancer, antiatherosclerotic, hypotensive, antiplatelet, and antidiabetic properties. Thus, the consumption of products made from chokeberries is of vital importance for health maintenance and protection. Nowadays, due to the growing prevalence of noncommunicable diseases and ubiquitous human exposure to numerous man-made and naturally occurring toxic substances, some of which are dangerous even at low amounts, it is very important to look for effective means of health protection. An important role in this regard may be played by A. melanocarpa berries; however, up to now the attention of scientists, nutritionists, and health practitioners has been focused mainly on the effectiveness of chokeberry products in the prevention and treatment of noncommunicable diseases, while only little attention has been paid to the possibility of their use to counteract the adverse health effects of exposure to xenobiotics. That is why in this review article the main interest has been focused on the possibility of using chokeberries in the protection against unfavorable health effects caused by the action of substances to which humans may be exposed environmentally and/or occupationally. The available experimental data indicate that not only the fruit but also the leaves of A. melanocarpa and their products may be effective means for prevention and treatment of the effects of toxic action of some xenobiotics in humans; however, further studies on this subject are necessary., (© 2016 Institute of Food Technologists®.)

Chronic kidney disease (CKD) is associated with disturbances in bone strength and metabolism. The alterations of the serotonergic system are also observed in CKD. We used the 5/6 nephrectomy model of CKD to assess the impact of peripheral serotonin and its metabolite- 5-hydroxyindoleacetic acid on bone biomechanical properties and metabolism in growing rats. The animals were sacrificed one and three months after nephrectomy. Biomechanical properties were determined on two different bone types: the cortical bone of the femoral diaphysis using three-point bending test and the mixed cortico-trabecular bone by the bending test of the femoral neck. Biomechanical tests revealed preserved cortical bone strength, whereas work to fracture (W) and yield load (Fy) of mixed cortico-trabecular bone were significantly lower in CKD compared to controls. Serum activity of alkaline phosphatase (ALP), a bone formation marker, and tartrate-resistant acid phosphatase (TRACP 5b) reflecting bone resorption, were similar in CKD and controls. ALP was associated with lower femoral stiffness and strength, and higher displacements and W. TRACP 5b was inversely associated with cortical Fu and W. The elevated peripheral serotonergic system in CKD was: inversely associated with stiffness but positively related to the displacements and W; inversely associated with cortical Fy but positively correlated with this parameter in cortico-trabecular bone; inversely associated with ALP in controls but positively correlated with this biomarker in CKD animals. In conclusion, this study demonstrates the distinct effect of mild degree of CKD on bone strength in rapidly growing rats. The impaired renal function affects the peripheral serotonin metabolism, which in turn may influence the strength and metabolism of bones in these rats. This relationship seems to be beneficial on the biomechanical properties of the cortico-trabecular bone, whereas the cortical bone strength can be potentially reduced., Competing Interests: The authors have declared that no competing interests exist.

Recently, we demonstrated in a rat model that consumption of a polyphenol-rich extract obtained from the berries of Aronia melanocarpa could protect from cadmium-induced disorders in bone turnover and changes in bone mineral status. The aim of this study was to investigate whether the osteoprotective effect of this extract is mediated by the oxidative defense system. Enzymatic and nonenzymatic antioxidants, total antioxidative and oxidative status, hydrogen peroxide, and markers of oxidative protein, lipid, and DNA damage were determined in bone tissue at the distal femoral epiphysis of female Wistar rats receiving 0.1 % aqueous A. melanocarpa extract (prepared from the lyophilized commercial extract containing 65.74 % of polyphenols) as the only drinking fluid and/or cadmium in the diet (1 and 5 mg/kg) for 3, 10, 17, and 24 months. The total oxidative and antioxidative status of the serum was also evaluated. The administration of A. melanocarpa extract provided significant protection from cadmium-induced oxidative stress in the bone and serum, and from lipid peroxidation and oxidative damage to the protein and DNA in the bone tissue. Numerous correlations were noted between indices of the oxidative/antioxidative bone status and markers of bone metabolism previously assayed in the animals receiving A. melanocarpa extract. The results allow the conclusion that the ability of A. melanocarpa extract to mediate the oxidative defense system and prevent oxidative modifications of protein, lipid, and DNA in the bone tissue plays an important role in its osteoprotective action under exposure to cadmium. The findings provide further evidence supporting our suggestion that chokeberry may be a promising natural agent for protection against the toxic action of cadmium in women chronically exposed to this metal., (Georg Thieme Verlag KG Stuttgart · New York.)

Compromised intestinal calcium absorption affecting a deterioration of bone state is a sign of coeliac disease. Experimental calcium-fortified gluten-free bread (GFB) of improved calcium bioavailability could increase calcium content in the diets of coeliac disease patients, allowing them to obtain the amount of calcium they need for therapeutic use. Prebiotics, including inulin-type fructans (IFs) have a beneficial effect on calcium bioavailability. In the present study, the in vitro model composed of the intestinal-like Caco-2 cells and the human intestinal bacteria (Lactobacillus, Enterococcus and Enterobacteriaceae) were used to analyse the effect of inulin and fructooligosaccharide (FOS) of different chain lengths, on calcium uptake and absorption from experimental GFB. Analysed IFs, especially short-chain FOS, significantly (p < 0.05) increased cellular calcium uptake from GFB digest and stimulated the intestinal bacteria applied in the cultures to the intensive synthesis of organic acids. In particular, the concentration of butyric, valeric and lactic acids increased significantly. Similarly, in the calcium absorption experiment, IFs increased the cellular calcium retention but concomitantly reduced its content in basolateral filtrates. The results obtained suggest that the applied IFs affected differentially calcium uptake and absorption from the experimental calcium-enriched GFB, therefore a further study is needed to assess whether these observations made in vitro contribute to IF effects on calcium absorption from experimental GFB in vivo.

Epidemiological studies provide a growing number of evidences that chronic exposure to relatively low levels of cadmium (Cd), nowadays taking place in industrialized countries, may cause health hazard. Thus, growing interest has been focused on effective ways of protection from adverse effects of exposure to this heavy metal. Because numerous effects to Cd's toxic action result from its prooxidative properties, it seems reasonable that special attention should be directed to agents that can prevent or reduce this metal-induced oxidative stress and its consequences in tissues, organs and systems at risk of toxicity, including liver, kidneys, testes, ears, eyes, cardiovascular system and nervous system as well as bone tissue. This review discusses a wide range of natural (plant and animal origin) and synthetic antioxidants together with many plant extracts (e.g. black and green tea, Aronia melanocarpa, Allium sativum, Allium cepa, Ocimum sanctum, Phoenix dactylifera, Physalis peruviana, Zingiber officinale) that have been shown to prevent from Cd toxicity. Moreover, some attention has been focused on the fact that substances not possessing antioxidative potential may also prevent Cd-induced oxidative stress and its consequences. So far, most of the data on the protective effects of the natural and synthetic antioxidants and plant extracts come from studies in animals' models; however, numerous of them seem to be promising preventive/therapeutic strategies for Cd toxicity in humans. Further investigation of prophylactic and therapeutic use of antioxidants in populations exposed to Cd environmentally and occupationally is warranted, given that therapeutically effective chelation therapy for this toxic metal is currently lacking.

Cosmetics, preparations repeatedly applied directly to the human skin, mucous membranes, hair and nails, should be safe for health, however, recently there has been increasing concern about their safety. Unfortunately, using these products in some cases is related to the occurrence of unfavourable effects resulting from intentional or the accidental presence of chemical substances, including toxic metals. Heavy metals such as lead, mercury, cadmium, arsenic and nickel, as well as aluminium, classified as a light metal, are detected in various types of cosmetics (colour cosmetics, face and body care products, hair cosmetics, herbal cosmetics, etc.). In addition, necessary, but harmful when they occur in excessive amounts, elements such as copper, iron, chromium and cobalt are also present in cosmetic products. Metals occurring in cosmetics may undergo retention and act directly in the skin or be absorbed through the skin into the blood, accumulate in the body and exert toxic effects in various organs. Some cases of topical (mainly allergic contact dermatitis) and systemic effects owing to exposure to metals present in cosmetics have been reported. Literature data show that in commercially available cosmetics toxic metals may be present in amounts creating a danger to human health. Thus, the present review article focused on the problems related to the presence of heavy metals and aluminium in cosmetics, including their sources, concentrations and law regulations as well as danger for the health of these products users. Owing to the growing usage of cosmetics it is necessary to pay special attention to these problems., (Copyright © 2015 John Wiley & Sons, Ltd.)

It was investigated, in a female rat model of low and moderate lifetime human exposure to cadmium (Cd), whether polyphenols from Aronia melanocarpa berries (chokeberry; AMP) may offer protection from this heavy metal-induced disorders in bone metabolism. For this purpose, numerous indices of bone formation (osteocalcin, alkaline phosphatase, osteoprotegerin) and resorption (carboxy-terminal cross-linking telopeptides of type I collagen, soluble receptor activator of nuclear factor-κB ligand) in the serum and/or distal femur epiphysis (trabecular bone region), as well as bone mineral status (volumetric bone mineral density of the femur and content of mineral components, including calcium, in the bone tissue at the distal femur epiphysis) were evaluated in female Wistar rats that received a 0.1% aqueous extract of AMP, as the only drinking fluid (prepared from lyophilized extract by Adamed Consumer Healthcare), and/or Cd in diet (1 and 5mg/kg) for 3, 10, 17, and 24 months. Examination of the phytochemical profile of the aronia extract revealed high content of polyphenols (612.40 ± 3.33 mg/g), including anthocyanins, proanthocyanidins, phenolic acids, and flavonoids. Among detected compounds anthocyanins were identified as dominating. The exposure to Cd, dose- and duration-dependently, enhanced resorption and inhibited formation of the bone tissue resulting in its decreased mineralization. The administration of AMP under the exposure to 1 and 5 mgCd/kg diet provided important protection from this heavy metal-induced disturbances in the bone turnover and changes in the bone mineral status, and the beneficial impact of polyphenols resulted from their independent action and interaction with Cd. These findings suggest that consumption of Aronia melanocarpa polyphenols may play a role in prevention against female skeleton damage due to chronic exposure to Cd and that chokeberry represents the good natural plant candidate for further investigations of its prophylactic use under environmental exposure to this heavy metal., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

It was investigated whether protective influence of zinc (Zn) against cadmium (Cd)-induced disorders in bone metabolism may be related to its antioxidative properties and impact on the receptor activator of nuclear factor (NF)-κΒ (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) system. Numerous indices of oxidative/antioxidative status, and Cd and Zn were determined in the distal femur of the rats administered Zn (30 and 60mg/l) or/and Cd (5 and 50mg/l) for 6months. Soluble RANKL (sRANKL) and OPG were measured in the bone and serum. Zn supplementation importantly protected from Cd-induced oxidative stress preventing protein, DNA, and lipid oxidation in the bone. Moreover, Zn protected from the Cd-induced increase in sRANKL concentration and the sRANKL/OPG ratio, and decrease in OPG concentration in the bone and serum. Numerous correlations were noted between indices of the oxidative/antioxidative bone status, concentrations of sRANKL and OPG in the bone and serum, as well as the bone concentrations of Zn and Cd, and previously reported by us in these animals (Brzóska et al., 2007) indices of bone turnover and bone mineral density. The results allow us to conclude that the ability of Zn to prevent from oxidative stress and the RANK/RANKL/OPG system imbalance may be implicated in the mechanisms of its protective impact against Cd-induced bone damage. This paper is the first report from an in vivo study providing evidence that beneficial Zn impact on the skeleton under exposure to Cd is related to the improvement of the bone tissue oxidative/antioxidative status and mediating the RANK/RANKL/OPG system., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Ethanol (Et) abusers may also be exposed to excessive amounts of cadmium (Cd). Thus, the study was aimed at estimating the influence of Et on the body turnover of Cd in a rat model reflecting excessive alcohol consumption in humans chronically exposed to moderate and relatively high levels of this metal. For this purpose, Cd apparent absorption, retention in the body and concentration in the blood, stomach, duodenum, liver, kidney, spleen, brain, heart, testis and femur as well as its fecal and urinary excretion in the rats exposed to 5 and 50mg Cd l(-1) (in drinking water; for 16 weeks from the fifth week of the animal's life) and/or Et (5 g kg(-1) b.w. per 24 h, by oral gavage; for 12 weeks from the ninth week of life) were estimated. Moreover, the duodenal, liver and kidney pool of the nonmetallothionein (Mt)-bound Cd was evaluated. The administration of Et during the exposure to 5 or 50mg Cd l(-1) increased Cd accumulation in the gastrointestinal tract and its urinary excretion, and decreased Cd concentration in the blood, femur and numerous soft tissues (including liver and kidney) as well as the total pool of this metal in internal organs. Et modified or not the pool of the non-Mt-bound Cd, depending on the level of treatment with this metal. The results show that excessive Et consumption during Cd exposure may decrease the body burden of this metal, at least partly, by its lower absorption and increased urinary excretion. Based on this study, it can be concluded that Cd concentration in the blood and tissues of alcohol abusers chronically exposed to moderate and relatively high levels of this metal may be lower, whereas its urinary excretion is higher than in their nondrinking counterparts. However, since Et is toxic itself, the decreased body burden of Cd owing to alcohol consumption does not allow for the conclusion that the risk of health damage may be lower at co-exposure to these xenobiotics. In a further study, it will be investigated how the Et-induced changes in the body status of Cd influence the effects of its toxic action., (Copyright © 2012 John Wiley & Sons, Ltd.)

This study investigated the influence of chlorfenvinphos (0.3 mg/kg bw/24 h corresponding to 0.02 LD50; orally by gastric gavage for 14 and 28 days) on lipid metabolism, and apoptotic and necrotic cells death in the brain of rats as the possible mechanism of neurotoxic action of organophosphate (OP) pesticides at low exposure. Total cholesterol (TCh), triglycerides (TG), phospholipids (PL), and free fatty acids (FFA) were determined and apoptotic, necrotic, and living cells were quantified in the brain. Moreover, the serum and brain acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were assayed as biomarkers of neurotoxicity. The treatment with chlorfenvinphos increased (duration dependently) the concentrations of TCh and TG and the ratio of TCh/PL, and decreased PL concentration. The prevalence of apoptotic and necrotic cells increased and that of the living brain cells depressed (by 10%) already after 14 days of the exposure. The brain activities of AChE and BChE decreased by 12% and 15%, and by 18% and 25% after 14 and 28 days, respectively, whereas the serum activities of these enzymes were inhibited (by 24% and 18%, respectively) only after the longer treatment. The changes in lipid metabolism and distribution of the living, apoptotic, and necrotic brain cells correlated with AChE and BChE activities in the serum and brain. The results show that chlorfenvinphos may disturb lipid metabolism and induce apoptosis and necrosis in the brain even at the exposure not affecting the serum activities of cholinesterases, and causing only moderate inhibition of their brain activities. Based on the findings it can be concluded that low repeated exposure to OP pesticides may influence the nervous system through disrupting the lipid profile of the nervous tissue and decreasing the number of the nervous cells., (Copyright © 2012 Elsevier GmbH. All rights reserved.)

It was investigated whether ethanol (Et) modifies the damaging impact of lead (Pb) on bone metabolism in a rat model reflecting excessive alcohol consumption by humans exposed to relatively high levels of this metal. For this purpose, markers of bone formation (osteocalcin, procollagen I, osteoprotegerin, alkaline phosphatase) and resorption (telopeptides of collagen I, soluble receptor activator of nuclear factor-κB ligand), calciotropic hormones (parathormone, calcitonin, 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D) in the serum, and the femur content of mineral (including calcium - Ca and inorganic phosphorus - P(i)) and organic components were estimated in the rats exposed to 500 mg Pb/l (in drinking water) or/and Et (5 g/kg b.wt./24 h, by oral gavage) for 12 weeks. Moreover, Ca and P(i) in the serum and urine, alkaline phosphatase in the bone tissue and Pb in the blood and femur were determined. The exposure to Pb or/and Et decreased bone formation and increased its resorption resulting in the bone demineralization. These effects were accompanied by destroying the hormonal regulation of mineral metabolism, and Ca and P(i) imbalance. The co-exposure to Pb and Et-induced disorders in bone metabolism were more advanced than those caused by Pb alone. Et co-administration increased Pb concentration in the blood and decreased its accumulation in the bone. This paper is the first report providing evidence that consumption of Et under exposure to Pb intensifies disorders in bone metabolism and that destroying of the receptor activator nuclear factor-κB (RANK)/RANK ligand/osteoprotegerin system is involved in the mechanisms of interactive action of these xenobiotics on the skeleton. The modifying impact of Et may be an effect of its independent osteotropic action and interaction with Pb. Based on the results it can be concluded that alcohol abuse by subjects excessively exposed to Pb considerably increases the risk of bone damage., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

It was investigated whether the ability of zinc (Zn) to prevent cadmium (Cd)-induced lipid peroxidation may be connected with its impact on glutathione peroxidase (GPx) activity and selenium (Se) concentration. GPx and Se were determined in the serum, liver and kidney of the rats that received Cd (5 or 50 mg/L) or/and Zn (30 mg/L) in drinking water for 6 months in whose the protective Zn impact was noted (Rogalska J, Brzóska MM, Roszczenko A, Moniuszko-Jakoniuk J. Enhanced zinc consumption prevents cadmium-induced alterations in lipid metabolism in male rats. Chem Biol Interact 2009;177:142-52). Moreover, dependences between these parameters, and indices of lipid peroxidation (F(2)-isoprostane, lipid peroxides, oxidized low density lipoprotein cholesterol) as well as concentrations of Cd and Zn were estimated. The supplementation with Zn during the exposure to 5 mg Cd/L entirely antagonized the Cd-induced increase in GPx activity and Se concentration in the liver and kidney, but not in the serum. Zn administration during the treatment with 50 mg Cd/L totally or partially prevented from the Cd-caused decrease in GPx activity and Se concentration in the serum, liver and kidney. At the higher level of Cd exposure, GPx activity in the serum and tissues positively correlated with Se concentration. Moreover, numerous correlations were noted between GPx and/or Se and the indices of lipid peroxidation. The results indicate that the protective impact of Zn against the Cd-induced lipid peroxidation during the relatively high exposure might be connected with its beneficial influence on Se concentration and GPx activity in the serum and tissues, whereas this bioelement influence at the moderate exposure seems to be independent of GPx and Se., (Copyright © 2011 Elsevier GmbH. All rights reserved.)

In the present paper, the hypothesis that low chronic exposure to cadmium (Cd) enhances the risk of long bone fractures was investigated in a female rat model simulating human lifetime exposure in non-Cd-polluted areas. For this purpose, the femur and both tibias of control female rats and those exposed to Cd (1 mg Cd I(-1) in drinking water for 24 months since weaning) were assigned to geometric, densitometric (bone mineral content, BMC, and density, BMD), radiographic and biomechanical studies as well as assessing their chemical composition. The exposure to Cd disturbed mineralization (decreased BMD and minerals content, including calcium, magnesium, zinc, copper and iron) and weakened the biomechanical strength of the femur and tibia, enhancing their fragility. The Z-score values for the BMD revealed osteopenia of the femur and tibia in 20 and 30% of the Cd-exposed female rats, respectively, and osteoporosis in 80 and 70%, respectively. In 30% of the Cd-exposed animals, femoral neck fracture was evident in the radiographic picture. The findings seem to confirm the hypothesis that a low exposure to Cd during the lifetime may be an important risk factor for osteoporosis and fractures of long bones, and especially for femoral neck fracture in elderly women. The results indicate that greater attention should be paid to Cd as an environmental risk factor for the increasing rate of osteoporosis and bone fractures in old population., (Copyright © 2011 John Wiley & Sons, Ltd.)

It was estimated, in a rat model of moderate and relatively high chronic human exposure to cadmium (Cd), whether enhanced zinc (Zn) consumption may prevent Cd-induced liver injury and if the possible protective effect of this bioelement depends on its intake. For this purpose, the structure and function of the liver of the rats that received Zn (30 and 60mg/l) or/and Cd (5 and 50mg/l) for 6months were evaluated. The treatment with Cd led to, dependent on the exposure level, pathological changes in the liver, including enhanced apoptosis and induction of inflammatory and necrotic processes. Moreover, the serum activities of hepatic marker enzymes (alanine transaminase and aspartate transaminase) and the concentration of proinflammatory cytokine - tumor necrosis factor α were increased. The supplementation with 30 and 60mg Zn/l (enhancing daily Zn intake by 79% and 151%, respectively) partially or totally prevented from some of the Cd-induced changes in the liver structure and function; however, it provided no protection from necrosis, and the administration of 60mg Zn/l during the higher Cd exposure even intensified this process. At both levels of Cd treatment, the use of 30mg Zn/l was more effective in preventing liver injury than that of 60mg Zn/l. The hepatoprotective impact of Zn may be explained, at least partly, by its antioxidative, antiapoptotic and anti-inflammatory action, ability to stimulate regenerative processes in the liver tissue, and indirect action resulting in a decrease in the liver pool of the non-metallothionein-bound Cd(2+) ions able to exert toxic action. The results provide strong evidence that enhanced Zn consumption may be beneficial in protection from Cd hepatotoxicity; however, its excessive intake at relatively high exposure to Cd may intensify liver injury., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

The aim of this study was to evaluate whether zinc (Zn) supplementation can protect from an enhanced risk of femoral neck fracture due to chronic exposure to cadmium (Cd). For this purpose, biomechanical properties of the neck and bone mineral density (BMD) at the proximal femur of rats receiving Cd (5 or 50mg/l) or/and Zn (30 or 60 mg/l) in drinking water for 6 and 12 months were evaluated. The exposure to 5 and 50mg Cd/l decreased the proximal femur BMD and affected biomechanical properties of the femoral neck. In the rats treated with 5mg Cd/l, weakening of the femoral neck strength was observed after 12 months, whereas at higher exposure--already after 6 months. The supplementation with 30 and 60 mg Zn/l, enhancing its daily intake by 68% and 138%, respectively, compared to the standard diet, had beneficial influence on the femoral neck biomechanical properties during the exposure to Cd, but it had no impact on the proximal femur BMD. Zn administration during the 12-month exposure to 5mg Cd/l totally prevented the weakening of the neck. Zn supplementation during the 6-month treatment with 50mg Cd/l entirely prevented the Cd-induced decrease in the neck fracture strength; however, at the longer exposure to Cd the protective effect of Zn was only partial. The beneficial Zn influence was independent on its dose. The results allow the conclusion that an increase in the daily intake of Zn during moderate and relatively high exposures to Cd can reduce femoral neck susceptibility to fracture. Based on the findings, it seems that enhanced Zn consumption in subjects chronically exposed to Cd may, at least partly, protect from the enhanced risk of femoral neck fracture., (Copyright © 2010 Elsevier GmbH. All rights reserved.)

It was investigated whether cadmium (Cd) may induce oxidative stress in the bone tissue in vivo and in this way contribute to skeleton damage. Total antioxidative status (TAS), antioxidative enzymes (glutathione peroxidase, superoxide dismutase, catalase), total oxidative status (TOS), hydrogen peroxide (H(2)O(2)), lipid peroxides (LPO), total thiol groups (TSH) and protein carbonyl groups (PC) as well as Cd in the bone tissue at the distal femoral epiphysis and femoral diaphysis of the male rats that received drinking water containing 0, 5, or 50mg Cd/l for 6 months were measured. Cd, depending on the level of exposure and bone location, decreased the bone antioxidative capacity and enhanced its oxidative status resulting in oxidative stress and oxidative protein and/or lipid modification. The treatment with 5 and 50mg Cd/l decreased TAS and activities of antioxidative enzymes as well as increased TOS and concentrations of H(2)O(2) and PC at the distal femur. Moreover, at the higher exposure, the concentration of LPO increased and that of TSH decreased. The Cd-induced changes in the oxidative/antioxidative balance of the femoral diaphysis, abundant in cortical bone, were less advanced than at the distal femur, where trabecular bone predominates. The results provide evidence that, even moderate, exposure to Cd induces oxidative stress and oxidative modifications in the bone tissue. Numerous correlations noted between the indices of oxidative/antioxidative bone status, and Cd accumulation in the bone tissue as well as indices of bone turnover and bone mineral status, recently reported by us (Toxicology 2007, 237, 89-103) in these rats, allow for the hypothesis that oxidative stress is involved in the mechanisms of damaging Cd action in the skeleton. The paper is the first report from an in vivo study indicating that Cd may affect bone tissue through disorders in its oxidative/antioxidative balance resulting in oxidative stress., (Copyright © 2010 Elsevier Inc. All rights reserved.)

The study investigated the risk of the femur and tibia fractures on a male rat model of low, moderate and relatively high human exposure to cadmium (1, 5 and 50mg Cd/l in drinking water for 12 months). Bone mineral density (BMD) and biomechanical properties at the proximal and distal femur, and femoral and tibial diaphysis as well as the bone content of mineral and organic components, were evaluated. The exposure to 1mg Cd/l caused only very subtle changes in biomechanical properties at the femoral neck and distal femur. In the rats treated with 5mg Cd/l, a decrease in the distal femur BMD (by 5.5%) and enhanced vulnerability to fracture at the femoral neck, distal femur, and tibia diaphysis were observed. At the highest Cd treatment, the BMD decreased (by 6.5-11%) and the biomechanical properties weakened at all regions of the femur and tibia. Moreover, a decrease in the femur and tibia content of mineral components (by 11.5% and 10%, respectively) and the tibia content of organic components (by 7%) was noted. The results seem to indicate that low chronic exposure to Cd can have no influence on the bone resistance to fracture, whereas moderate (and particularly relatively high) exposure seriously increases the risk of fracture of long bones in males. The observations, together with our findings on an analogous female rat model, provide evidence that males are less vulnerable to Cd-induced demineralization and weakening of biomechanical properties of the femur and tibia than females., (Copyright © 2010 Elsevier B.V. All rights reserved.)

The study was aimed to estimate whether rat's exposure to cadmium (Cd; 50mg/l in drinking water for 12 weeks) and/or ethanol (EtOH; 5g/kg b.wt./24h p.o. for 12 weeks), noted by us to induce oxidative stress and stimulate lipid peroxidation, can cause oxidative damage to proteins and DNA, and whether and to what extent the effects of co-exposure differ from those observed under the treatment with each substance alone. Protein carbonyl groups (PC) and protein thiol groups (PSH) in the serum, liver and kidney, as markers of oxidative protein damage, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in the serum, as a marker of DNA oxidation, were determined. The exposure to Cd or/and EtOH led to oxidative protein damage (increased PC and decreased PSH concentrations in the serum and/or liver), and to DNA oxidation (increased 8-OHdG concentration in the serum). The effects were more advanced at the co-exposure than at the treatment with each substance alone. The more serious damage to proteins and DNA at the co-exposure to Cd and EtOH seems to be the effect of independent action of both xenobiotics. The results of the present paper together with our recent findings in the same rats seem to indicate that at co-exposure to Cd and EtOH proteins and DNA may be more vulnerable to oxidation than lipids. The paper is the first report suggesting that excessive EtOH consumption during exposure to Cd may increase the risk of health damage via enhancing protein and DNA oxidation.

It has been investigated, based on a rat model of human exposure to cadmium (Cd), whether zinc (Zn) supplementation may prevent Cd-induced alterations in lipid metabolism. For this purpose, the concentrations of free fatty acids (FFA), phospholipids (PL), triglycerides (TG), total cholesterol (TCh), and high and low density lipoprotein cholesterol (HDL and LDL, respectively) as well as the concentrations of chosen indices of lipid peroxidation such as lipid peroxides (LPO), F2-isoprostane (F2-IsoP) and oxidized LDL (oxLDL) were estimated in the serum of male Wistar rats administered Cd (5 or 50mg/l) or/and Zn (30 or 60mg/l) in drinking water for 6 months. The exposure to 5 and 50mg Cd/l resulted in marked alterations in the lipid status reflected in increased concentrations of FFA, TCh, LDL, LPO, F2-IsoP and oxLDL, and decreased concentrations of PL and HDL in the serum. The concentrations of LDL, LPO, F2-IsoP and oxLDL were more markedly enhanced at the higher Cd dosage. The supplementation with Zn during the exposure to 5 and 50mg Cd/l entirely prevented all the Cd-induced changes in the serum concentrations of the estimated lipid compounds and indices of lipid peroxidation, except for the F2-IsoP for which Zn provided only partial protection. Based on the results it can be concluded that Zn supplementation during exposure to Cd may have a protective effect on lipid metabolism consisting in its ability to prevent hyperlipidemia, including especially hypercholesterolemia, and to protect from lipid peroxidation. The findings seem to suggest that enhanced dietary Zn intake during Cd exposure, via preventing alterations in the body status of lipids may, at least partly, protect against some effects of Cd toxicity, including oxidative damage to the cellular membranes and atherogenic action. The paper is the first report suggesting protective impact of Zn against proatherogenic Cd action on experimental model of chronic moderate and relatively high human exposure to this toxic metal.

The present study was aimed at estimate, based on the rat model of human moderate and relatively high chronic exposure to cadmium (Cd), whether zinc (Zn) supplementation may prevent Cd-induced weakening in the bone biomechanical properties. For this purpose, male Wistar rats were administered Cd (5 or 50 mg/l) or/and Zn (30 or 60 mg/l) in drinking water for 6 and 12 months. Bone mineral density (BMD) and biomechanical properties (yield load, ultimate load, post-yield load, displacement at yield and at ultimate, stiffness, work to fracture, yield stress, ultimate stress and Young modulus of elasticity) of the femoral distal end and femoral diaphysis were examined. Biomechanical properties of the distal femur were estimated in a compression test, whereas those of the femoral diaphysis -- in a three-point bending test. Exposure to Cd, in a dose and duration dependent manner, decreased the BMD and weakened the biomechanical properties of the femur at its distal end and diaphysis. Zn supplementation during Cd exposure partly, but importantly, prevented the weakening in the bone biomechanical properties. The favorable Zn influence seemed to result from an independent action of this bioelement and its interaction with Cd. However, Zn supply at the exposure to Cd had no statistically significant influence on the BMD at the distal end and diaphysis of the femur. The results of the present paper suggest that Zn supplementation during exposure to Cd may have a protective influence on the bone tissue biomechanical properties, and in this way it can, at least partly, decrease the risk of bone fractures. The findings seem to indicate that enhanced dietary Zn intake may be beneficial for the skeleton in subjects chronically exposed to Cd.

To estimate exposure to cadmium (Cd) and lead (Pb) through cigarette smoking, the concentrations of both metals in the blood or/and urine of smokers (20 cigarettes or more per day for 10 years or longer) and their non-smoking counterparts inhabiting an environmentally unpolluted area (Bialystok, Poland) were evaluated, as well as Cd and Pb contents in the cigarette brands (produced in Poland) smoked by the participants, including intact cigarettes, pre-smoking (tobacco, paper and filter) and post-smoking (butt, ash and smoke) cigarette components. Blood and urinary Cd concentrations in the smokers have been already reported by us to be 2-4 times higher than in the non-smokers (Galazyn-Sidorczuk et al. Polish Journal of Environmental Studies, 13 (Suppl.1):91-95, 2004). All the other measurements are the subject of the present paper. Pb concentration in the blood of the cigarette smokers (52.12 +/- 15.51 microg l(-1)) was higher by 29% than in the non-smokers (40.42 +/- 11.19 microg l(-1)). The mean Cd and Pb contents in the cigarettes were 0.6801 +/- 0.1765 and 0.6853 +/- 0.0746 microg per cigarette, respectively. Under cigarette burning, performed using a machine for self-acting burning, on average 33% of Cd and 11% of Pb present in the whole cigarette was released into the smoke. For Cd, unlike Pb, there was a high positive correlation between the metal content in cigarettes and tobacco and its release into the smoke. Moreover, the subjects smoking cigarettes containing the highest Cd amount had higher blood Cd concentration than smokers of other cigarette brands. The results give clear evidence that in the case of inhabitants of areas unpolluted with Cd and Pb habitual cigarette smoking, due to tobacco contamination, creates a serious source of chronic exposure to these metals, especially to Cd.

The study was aimed at investigating vitamin E and vitamin C concentrations in a liver and kidney as well as their involvement in the mechanism of peroxidative action of lead (Pb) and ethanol (EtOH) in these organs in rats receiving 500 mg Pb/l (in drinking water) or/and 5 g EtOH/kg body wt./24h (p.o.) for 12 weeks. The exposure to Pb and EtOH alone and in combination led to a decrease in vitamin E concentration in the liver compared to the control group (by 30%, 26% and 50%, respectively). The decrease in the liver vitamin E concentration in the rats co-exposed to Pb and EtOH was more marked than in those separately treated with these xenobiotics. The treatment with Pb alone and in combination with EtOH led to a decrease in vitamin E concentration in the kidney (by 13% and 21%, respectively). The liver vitamin C concentration decreased as a result of exposure to EtOH, both separately (by 17%) and in combination with Pb (by 11%). The kidney vitamin C concentration increased in the rats exposed to EtOH alone (by 10%), whereas in those treated with Pb, both separately and in combination with EtOH it decreased (by 26% and 6%, respectively). ANOVA/MANOVA analysis revealed that the changes in vitamin E concentration in the liver and kidney at co-exposure to Pb and EtOH resulted from their independent action, whereas those in vitamin C were due to an independent action of these xenobiotics (EtOH in the liver, Pb and EtOH in the kidney) and an interaction between them. There was no correlation between vitamins E and C concentrations in the liver and kidney. The liver concentration of vitamin E and the liver and kidney concentration of vitamin C negatively correlated with malondialdehyde concentration (MDA, lipid peroxidation index) in these organs. Based on the results of the present study and our previous findings in this experimental rat model it can be hypothesized that vitamins E and C are involved in the mechanism of peroxidative action of Pb and EtOH in the liver and kidney, both at separate and combined exposure. The probable protective involvement of vitamins E and C in the damaging action of EtOH and Pb may be related to scavenging of free radicals directly and indirectly generated by these xenobiotics.

The aim of the present study is to investigate, based on the rat model of moderate and relatively high human exposure to cadmium (Cd), whether zinc (Zn) supplementation may prevent Cd-induced disorders in bone metabolism. For this purpose, male Wistar rats received Cd (5 and 50mg/l) or/and Zn (30 and 60mg/l) in drinking water for 6 and 12 months. Bone densitometry and biochemical markers of bone turnover were used to assess the effects of Cd or/and Zn. Bone mineral content (BMC) and density (BMD) were measured in the femur. Serum osteocalcin (OC) and alkaline phosphatase in trabecular (bT-ALP) and cortical (bC-ALP) bone were determined as bone formation markers, and carboxy-terminal cross-linking telopeptides of type I collagen (CTX) in serum were measured as bone resorption marker. Serum concentration of calcium (Ca) and its renal handling, as well as Zn and Cd concentrations in the serum/blood, urine and femur were evaluated as well. The exposure to 5 and 50mg Cd/l (0.340+/-0.026 and 2.498+/-0.093mg Cd/kg body wt/24h, respectively), in a dose and duration dependent manner, affected bone turnover (inhibited bone formation and stimulated its resorption) and disturbed bone mineralization (decreased BMC, BMD and Zn concentration). Zn supply at the concentration of 30 and 60mg/l (1.904+/-0.123 and 3.699+/-0.213mg/kg body wt/24h, respectively) during Cd exposure influenced the Cd-induced disorders in bone metabolism. Zn administration to the Cd-exposed rats enhanced the bone ALP activity and prevented Cd-induced bone resorption, but had no statistically significant effect on BMC and BMD; however, mean values of the densitometric parameters in the rats receiving both Cd and Zn were higher than in those treated with Cd alone. Moreover, Zn supplementation at both levels of Cd exposure was found to prevent Cd accumulation in the femur and the Cd-induced decrease in bone Zn concentration. The results of the present study allow the conclusion that Zn supplementation during Cd exposure may partly protect from disorders in bone metabolism. The influence of Zn may be accompanied by its ability to prevent Cd-induced Zn deficiency and to decrease Cd accumulation in bone tissue. The findings seem to indicate that enhanced dietary intake of Zn in subjects chronically exposed to moderate and relatively high Cd levels may have a protective influence on the skeleton.

The involvement of low-molecular thiols, such as reduced glutathione (GSH) and metallothionein (Mt), in the mechanisms of the peroxidative action of lead (Pb) and ethanol (EtOH) in liver and kidney was investigated on rats treated with 500 mg Pb/l (in drinking water) and 5 g EtOH/kg body wt./24h (p.o.), alone and in conjunction with each other for 12 weeks. Beside of GSH and Mt, concentration of total and non-protein SH groups (TSH and NPSH, respectively) in these organs as well as the blood activity of dehydratase of delta-aminolevulinic acid (delta-ALAD) and the urinary concentration of delta-aminolevulinic acid (delta-ALA) were determined. The exposure to Pb and EtOH alone and in conjunction with each other led to a decrease in the blood delta-ALAD activity and an increase in the urinary delta-ALA concentration, and these effects were more markedly advanced at co-exposure. In the liver and kidney of rats treated with Pb and/or EtOH, a decrease in concentrations of GSH and NPSH was noted, compared to control. However, in the Pb+EtOH group, only the liver concentrations of NPSH and GSH were lower also compared to the Pb and EtOH groups. The liver concentration of TSH decreased in the rats exposed to EtOH alone and in conjunction with Pb, whereas the kidney concentration of TSH decreased only at co-exposure to Pb and EtOH. Mt concentration was unchanged except for an increase in the liver in the Pb and Pb+EtOH groups. Two-way analysis of variance (ANOVA/MANOVA) revealed that the changes noted at the co-exposure to Pb and EtOH resulted from an independent action of the two xenobiotics as well as from their interactive action. Negative correlations noted between the liver and kidney concentrations of GSH and/or NPSH and recently reported malondialdehyde (MDA, an indicator of lipid peroxidation) concentration in both organs of those rats indicate the relationship between the content of SH groups and the intensity of the Pb and/or EtOH-induced lipid peroxidation. The results allow for the conclusion that the decrease in the liver and kidney concentrations of GSH and NPSH are involved in the mechanisms of the peroxidative action of Pb and EtOH alone and at co-exposure in these organs.