Malgorzata M. Brzóska

The influence of calcium content in diet on cumulation and toxicity of cadmium in the organism.

Abstract Voluminous literature data show that great interdependence exists between the nutrition status of the organism and the degree of accumulation and toxicity of heavy metals. In this work, the connection between dietary calcium and cadmium toxicity is discussed from the toxicological point of view. Cadmium is one of the most dangerous occupational and environmental poisons. The intake of diet containing an inappropriate amount of calcium causes increased absorption of cadmium from the gastrointestinal tract and increased accumulation of this metal in the organism, finally leading to enhancement of cadmium toxic action. The large intake of calcium protects against absorption, cumulation and toxicity of this heavy metal. Interactions between calcium and cadmium may take place at different stages of their metabolism (absorption, distribution in the organism, elimination) and cadmium may interfere with the biological functions of Ca2+ ions.

ENHANCED ZINC CONSUMPTION PREVENTS CADMIUM-INDUCED ALTERATIONS IN LIPID METABOLISM IN MALE RATS

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.

Effect of zinc supplementation on bone metabolism in male rats chronically exposed to cadmium.

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.

Protective effect of zinc against cadmium hepatotoxicity depends on this bioelement intake and level of cadmium exposure: a study in a rat model

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.

Beneficial effect of zinc supplementation on biomechanical properties of femoral distal end and femoral diaphysis of male rats chronically exposed to cadmium

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.

The effect of zinc supply on cadmium-induced changes in the tibia of rats

It has been determined that zinc supplementation (240 microg Zn/ml) during (for 12 weeks) or after (for 2 weeks) cadmium exposure (50 microg Cd/ml for 12 weeks) can prevent the accumulation and toxic action of Cd in the tibia of rats. The exposure to Cd led to disturbances in bone metabolism reflected by changes in the chemical composition of bone and decreased bone mineral density (osteomalacian changes). The Zn supply in conditions of Cd intoxication completely prevented the Cd-induced increase in percentage of water content and decrease in tibia ash weight, ash weight/dry weight, non-org. comp./org. comp., Zn content and concentration. Moreover, Zn partly protected from the decrease in Ca concentration and content, percentage of non-organic components content, Ca/wet weight, Ca/ash weight and Ca/dry weight. Zn administered after Cd exposure partly, but not completely, protected from Cd-induced decrease in percentage of non-organic components content, Ca/wet weight as well as Ca content and concentration. This protective effect on bone was most evident when Zn was administered during Cd exposure. But Zn, independently of the manner of its administration, did not prevent Cd accumulation in the tibia. Our results suggest that Zn supply in conditions of simultaneous exposure can prevent Cd-induced bone loss to some extent, and used after Cd treatment can give therapeutic benefits.

Mechanical Properties of Femoral Diaphysis and Femoral Neck of Female Rats Chronically Exposed to Various Levels of Cadmium

The effect of chronic exposure to cadmium (Cd) on the mechanical properties of femoral diaphysis and femoral neck was investigated on a rat model of human exposure. Three-week-old female Wistar rats were exposed to Cd in drinking water at concentrations of 1, 5, 50, or 100 mg/L for 12 months. Biomechanical properties of the femoral diaphysis were evaluated in a three-point bending test and those of the femoral neck in a bending test with vertical loading of the head. Bone mineral content (BMC) and bone mineral density (BMD) at the whole femur, and BMD at the diaphysis and proximal femur (head and neck region) of the Cd-treated rats decreased in a dose-dependent manner, except for the diaphyseal BMD at a Cd concentration of 1 mg/L. Exposure to Cd concentrations of 1 and 5 mg/L had only little effect on the diaphyseal mechanical properties (decreased yield load with unchanged bending strength, stiffness, yield stress, ultimate stress, and Young modulus), whereas the bending strength and stiffness of the neck decreased and the yield load clearly tended to decline or declined. The effect of Cd at the two locations was more marked in the 50 and 100 mg/L groups, and changes in the bone geometry were observed in these animals. The results clearly revealed that chronic, even low-level, exposure to Cd results in demineralization and weakening of the femur. The femoral neck seems to be more vulnerable than the diaphysis to failure from Cd. We conclude that environmental exposure to Cd may be an important risk factor for femoral neck fracture.

Metals in cosmetics: implications for human health

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

The involvement of oxidative stress in the mechanisms of damaging cadmium action in bone tissue: A study in a rat model of moderate and relatively high human exposure

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.

Protective effect of zinc supplementation against cadmium-induced oxidative stress and the RANK/RANKL/OPG system imbalance in the bone tissue of rats.

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.