Tissue-specific accumulation of cadmium and its effects on antioxidative responses in Japanese flounder juveniles

This study investigated the accumulation of cadmium (0-8 mg Cd L⁻¹) and its toxicological effects on oxidative stress biomarkers in different tissues of Japanese flounder juveniles. Following Cd exposure for 28 d, accumulation of Cd in fish was dose-dependent and tissue-specific, with the greatest accumulation in the liver, followed by the kidney, gill, and muscle. Although the gill and liver mounted active antioxidant responses at ≥4 mg L⁻¹ Cd including a decrease in glutathione level and GST and GPx activities, the antioxidant response failed to prevent lipid peroxidation induction in these organs. In the kidney, increased GPx and GST activities and decreased SOD activity were observed in fish exposed to high Cd concentrations, but LPO levels did not significantly differ among the exposure concentrations. The gill was most sensitive to oxidative damage, followed by the liver; the kidney was the least affected tissue.     

Biochemical responses of <Emphasis Type="Italic">Lemna minor</Emphasis> experimentally exposed to cadmium and zinc

The effects of 5 μM cadmium (Cd), a non-essential toxic element and 25 and 50 μM zinc (Zn), an essential micronutrient, were investigated in aquatic plant Lemna minor L. after 4 and 7 days of exposure to each metal alone or to their combinations. Both metals showed tendency to accumulate with time, but when present in combination, they reduced uptake of each other. Cd treatment increased the lipid peroxidation and protein oxidation indicating appearance of oxidative stress. However, Zn supplementation in either concentration reduced values of both parameters, while exposure to Zn alone resulted in elevated level of lipid peroxidation and protein oxidation but only on the 7th day. Enhanced DNA damage, which was found on the 4th day in plants treated with Cd alone or in combination with Zn, was reduced on the 7th day in combined treatments. Higher catalase activity obtained in all treated plants on the 4th day of experiment was reduced in Zn-treated plants, but remained high in plants exposed to Cd alone or in combination with Zn after 7 days. Cd exposure resulted in higher peroxidase activity, while Zn addition prominently reduced peroxidase activity in the plants subjected to Cd stress. In conclusion, Cd induced more pronounced oxidative stress and DNA damage than Zn in applied concentrations. Combined treatments showed lower values of oxidative stress parameters—lipid peroxidation, protein oxidation and peroxidase activity as well as lower DNA damage, which indicates alleviating effect of Zn on oxidative stress in Cd-treated plants.     

Cross-tolerance to hyperoxia following cadmium aerosol pretreatment

Preexposure of male Lewis rats to Cd aerosols (1.6 mg Cd/m3, 3 hr/day, 5 days/week, for 4 weeks) has been found to produce a marked degree of tolerance to hyperoxia (greater than 96% O2). Cd-pretreated animals were still alive after 8 days of continuous exposure to oxygen. In contrast, hyperoxia was fatal to all air-preexposed animals within 54-62 hr. Lungs of Cd-pretreated animals were characterized by hyperplasia and/or hypertrophy of the type II alveolar cell compartment which may have enabled them to more rapidly repair oxidant damage resulting from hyperoxia. Cd pretreatment augmented enzymatic antioxidant enzyme activities, including total lung Se-dependent glutathione peroxidase, catalase, glutathione reductase, and Mn-superoxide dismutase, and caused elevations in pulmonary nonprotein thiols and metallothionein (MT). MT, a thiol-rich, low-molecular-weight protein, was 400-fold higher in Cd-pretreated animals and bound more than 80% of the total Cd in the lung. We have hypothesized that MT serves as an expendable yet renewable cellular target for free radical damage during oxygen exposure. A systemic acute-phase response, characterized by alterations in plasma Zn and Cu concentrations and increased ceruloplasmin oxidase activity, was initiated in Cd-pretreated animals by the fourth day of hyperoxia. This response was accompanied by improvement in pulmonary status and extensive pulmonary repair.     

Differential protein expression profiles in anterior gills of Eriocheir sinensis during acclimation to cadmium

Using a proteomic approach, we characterized different protein expression profiles in anterior gills of the Chinese mitten crab, Eriocheir sinensis, after cadmium (Cd) exposure. Two experimental conditions were tested: (i) an acute exposure (i.e. 500 microg Cd l(-1) for 3 days) for which physiological, biochemical and ultrastructural damage have been observed previously; (ii) a chronic exposure (i.e. 50 microg Cd l(-1) for 30 days) resulting in physiological acclimation, i.e. increased resistance to a subsequent acute exposure. Two-dimensional gel electrophoresis (2-DE) revealed six protein spots differentially expressed after acute, and 31 after chronic Cd exposure. From these spots, 15 protein species were identified using MS/MS micro-sequencing and MS BLAST database searches. Alpha tubulin, glutathione S-transferase and crustacean calcium-binding protein 23 were down-regulated after an acute exposure, whereas another glutathione S-transferase isoform was up-regulated. Furthermore, analyses revealed the over-expression of protein disulfide isomerase, thioredoxin peroxidase, glutathione S-transferase, a proteasome subunit and cathepsin D after chronic exposure. Under the same condition, ATP synthase beta, alpha tubulin, arginine kinase, glyceraldehyde-3-phosphate dehydrogenase and malate dehydrogenase were down-regulated. These results demonstrate that acute and chronic exposure to waterborne Cd induced different responses at the protein expression level. Protein identification supports the idea that Cd mainly exerts its toxicity through oxidative stress induction and sulfhydryl-group binding. As a result, analyses showed the up-regulation of several antioxidant enzymes and chaperonins during acclimation process. The gill proteolytic capacity seems also to be increased. On the other hand, the clearly decreased abundance of several enzymes involved in energy transfer suggests that chronic metal exposure induced an important metabolic reshuffling.     

In vitro effects of simultaneous exposure to platinum and cadmium on the activity of antioxidant enzymes and DNA damage and potential protective effects of selenium and zinc

Circulating platinum (Pt) is detectable in the blood of Pt-treated cancer patients for over a decade after the treatment. Prolonged exposure to Pt, in combination with adverse compounds from nutrition and lifestyle, such as cadmium (Cd), could increase the risk from second cancers. The aim of this study was to investigate the effects of simultaneous exposure to Cd- and Pt-compounds on oxidative and DNA damage and the possible protective effects of zinc (Zn) and selenium (Se). The aqueous solutions of PtCl₄, CdCl_2?×_?H₂O, ZnCl₂ and Na₂SeO₃ were added, alone or in combination, to whole blood and isolated erythrocytes to produce the final concentrations of 2000?μg/L of Pt, 8?μg/L of Cd, 100?μg/L of Se, and 1000?μg/L of Zn. The activity of copper, zinc-superoxide dismutase, glutathione peroxidase and glutathione in whole blood was determined after 1?h exposure in in vitro conditions. The induction of DNA strand-breaks in human peripheral blood leukocytes was determined with the alkaline comet assay after 24?h exposure. Exposure to Pt and/or Cd decreased the activities of antioxidant enzymes and elevated DNA damage compared to control. A statistically significant change in the activity of both enzymes and in the induction of DNA strand-breaks was observed in the cells treated with Pt?+?Cd combination, while the addition of Se and/or Zn resulted in partial recovery of these effects. The results indicate that combined exposure to Pt and Cd could disrupt antioxidant protection of the organism and increase DNA damage, whereas Se and Zn could partially ameliorate these harmful effects.     

Biochemical, histological and ultrastructural alterations of the alimentary system in the freshwater crab Sinopotamon henanense subchronically exposed to cadmium

Cadmium (Cd) is one of the toxic metals in the aquatic environment. We investigated the effects of Cd on the digestive enzymes, antioxidant enzymes, malondialdehyde (MDA) content and morphology of the hepatopancreas and intestine in the freshwater crab Sinopotamon henanense. Crabs were exposed to sublethal Cd concentrations of 0, 0.725, 1.450 and 2.900 mg/L for 21 days. After Cd exposure, the activities of maltase, amylase and trypsin of two tissues were lower than the control. The activities of superoxide dismutase, catalase and glutathione peroxidase in the hepatopancreas and intestine were decreased, and the MDA concentration increased in all of the treated groups, over the experimental period. The results of light and transmission electron microscopy showed that 2.900 mg/L of Cd exposure caused profound morphological damages in the hepatopancreas and midgut. After exposure, histological abnormalities of two tissues were discovered, including cellular swelling and necrosis. Additionally, alterations in microvilli, nucleus, mitochondria, rough endoplasmic reticulum as well as Golgi complex in epithelial cells of two tissues were observed. This may be due to antioxidant enzymes activities that were reduced by Cd in the alimentary system of the crabs, and led to membrane lipid peroxidation. The membrane structure was destroyed, and caused further tissue damage, which likely made the alimentary system unable to secrete digestive enzymes, leading to further reduction of digestive enzymes.     

Using an integrated approach to link biomarker responses and physiological stress to growth impairment of cadmium-exposed larval topsmelt

In this study, we used an integrated approach to determine whether key biochemical, cellular, and physiological responses were related to growth impairment of cadmium (Cd)-exposed larval topsmelt (Atherinops affinis). Food intake (Artemia franciscana nauplii), oxygen consumption rates, apoptotic DNA fragmentation (TUNEL assay), and metallothionein (MT)-like protein levels, were separately measured in relation to growth of larval topsmelt aqueously exposed to sublethal doses of Cd for 14 days. Cadmium accumulation and concentrations of abundant metals were also evaluated in a subset of fish. Fish in the highest Cd treatments (50 and 100 ppb Cd) were smaller in final mean weight and length, and consumed fewer A. franciscana nauplii than control fish. Food intake was positively correlated with final weight of larval topsmelt in Cd and control treatments; food intake increased as final weight of the fish increased. Oxygen consumption rates were positively correlated with Cd concentration and mean oxygen consumption rates were inversely correlated with final mean weight of topsmelt; the smallest fish were found in the highest Cd treatment and were respiring at higher rates than control fish. Apoptotic DNA fragmentation was concentration-dependent and was associated with diminished growth. Apoptotic DNA fragmentation was elevated in the gill of fish exposed to 50 ppb Cd, and in the gut, gill, and liver of fish exposed to 100 ppb Cd. Metallothionein (MT)-like protein levels in fish from 100 ppb Cd treatments were significantly higher than those in other treatments. Oxygen consumption rates may have increased as a compensatory response to Cd exposure. However, it is likely that the energy produced was allocated to an increased metabolic demand due to apoptosis, MT synthesis, and changes in ion regulation. This diversion of energy expenditures could contribute to growth impairment of Cd-exposed fish.     

Morphological and biochemical perturbations in rat erythrocytes following in vitro exposure to Fenvalerate and its metabolite.

Erythrocytes are a convenient model to understand the membrane oxidative damage induced by various xenobiotic-prooxidants. In this investigation, we have examined the potency of Fenvalerate (FEN) and its metabolite, p-chlorophenyl isovaleric acid (p-CPIA) to induce oxidative stress response in rat erythrocytes in vitro in terms of lipid peroxidation and effects on selected antioxidant enzymes. Susceptibility of erythrocytes to FEN exposure was further investigated in terms of morphological alterations by scanning electron microscopy and protein damage by gel electrophoresis of erythrocyte ghosts. Following in vitro exposure, FEN caused a significant induction of oxidative damage in erythrocytes at concentrations beyond 0.1 mM as evidenced by increased thiobarbituric acid reactive substances (TBARS) levels. The response was both concentration and time dependent. At higher concentrations, significant decreases in the activities of vital antioxidant enzymes viz., catalase, superoxide dismutase, glutathione transferase and glutathione reductase were also discernible clearly suggesting the potency of both, parent compound and its metabolite to induce oxidative stress in erythrocytes. Scanning electron micrographs of erythrocytes following FEN exposure at higher concentrations revealed various degrees of distortion in shape and ruptured membranes. Furthermore, gel electrophoresis studies revealed consistent and significant aggregation of only band 3 protein in erythrocyte membranes exposed to either FEN or p-CPIA at higher concentrations. These in vitro findings show that FEN and its metabolite have the propensity to cause significant oxidative damage in rat erythrocytes, which is associated with marked damage to membrane proteins. These data suggest that both structural and functional perturbations may ensue in erythrocytes following exposure to FEN at higher concentrations under in vivo situations.     

Intraspecific differences in cadmium tolerance of <Emphasis Type="Italic">Nitzschia palea</Emphasis> (Kützing) W. Smith: a biochemical approach

Intraspecific variability occurs in all types of organisms and is a driving force to speciation, conferring genotypic and phenotypic differences that enable adaptive responses to sub-lethal stimuli such as exposure to pollutants (including cadmium, Cd). Thus, differences in biochemical parameters are expected among isolates of the same species. Studying the extent of these differences throughout a stress range, will provide information for the development of approaches to mitigate habitat contamination. This work was designed to identify possible differences in Cd tolerance of five isolates of the freshwater diatom Nitzschia palea from different sampling sites. Each isolate was exposed to five increasing Cd concentrations during 10 days. Growth inhibition was assessed and intracellular accumulation of Cd was quantified. Superoxide dismutase and catalase activities were determined. Glutathione as well as lipid peroxidation (LPO) and intracellular protein content were quantified. The results obtained identified intraspecific differences among isolates. These differences were associated with different approaches of coping with Cd stress. Higher intracellular Cd concentrations induced lower tolerance in isolates, since antioxidant mechanisms were unable to fight effectively against higher oxidative stress. Reversely, lower intracellular accumulation of Cd induced lower oxidative damage and allowed cells to better tolerate exposure to Cd. LPO emerged as an excellent marker of oxidative stress in N. palea and its use can differentiate isolates according to their tolerance.     

Response of antioxidant enzymes, ascorbate and glutathione metabolism towards cadmium in hyperaccumulator and nonhyperaccumulator ecotypes of Sedum alfredii H

Hydroponics studies were conducted to investigate the antioxidant adaptations, ascorbate and glutathione metabolism in hyperaccumulating ecotype of Sedum alfredii (HE) exposed to high Cd environment, when compared with its nonhyperaccumulating ecotype (NHE). Exposure to Cd induced a burst of oxidative stress in both ecotypes which was evident by the sharp increase in hydrogen peroxide (H(2)O(2)) contents and lipid peroxidation. Buthionine sulfoximine (BSO), an inhibitor of glutathione (GSH) synthesis, did not affect H(2)O(2) concentrations as well as growth of both ecotypes in the absence of Cd. However, compared with Cd application alone, BSO combined with Cd treatment caused a substantial augmentation of H(2)O(2) accumulation accompanied by a reduction in Cd concentrations in roots and leaves of HE at the end of treatment, which may rule out the possibility that GSH biosynthesis may play an important role as a signal of the stress regulation. No efficient and superior enzymatic antioxidant defense mechanisms against Cd-imposed oxidative stress existed in both NHE and HE, but the essential nonenzymatic components like ascorbic acid (AsA) and GSH played a prominent role in tolerance against Cd. Cadmium stimulated a notable rise in AsA concentration in both ecotypes soon after the application of treatment. A preferential Cd-stress response in HE was suggested to changes in the GSH pool, where acclimation was marked by increased GSH concentrations.     

Antimicrobial activity of isolate HL-12 against Clavibacter michiganensis subsp. michiganensis in the presence of cadmium

An actinomycete, strain HL-12, that was isolated from a farmland on the Huajiachi campus of Zhejiang University was capable of inhibiting the growth of Clavibacter michiganensis subsp. michiganensis (Cmm) and was identified as a member of Streptomyces. Its antimicrobial activity against Cmm was measured using the agar plate sensitivity method in pure culture and evaluated by the inhibition ratio of Cmm in soil. The inhibitory activity of strain HL-12 against Cmm following exposure to low concentrations of Cd was greater than the inhibitory activity following exposure to high concentrations of Cd both in liquid culture and in soil. A stronger inhibition was also seen following a 24 h preculture in the presence of Cd in liquid culture. The growth of Cmm in soil was stimulated at low concentrations of Cd (<5.0 mg Cd kg⁻¹ dry soil) but inhibited when cultured in high concentrations of Cd (5.0 and 10.0 mg Cd kg⁻¹ dry soil). A higher inhibition ratio of strain HL-12 against Cmm, which was over 40% after soil incubation for 2 weeks, was observed following exposure to low concentrations of Cd (<5.0 mg Cd kg⁻¹ dry soil).     

Combined effects of γ-irradiation and cadmium exposures on osteoblasts in vitro

The combined effects of γ-irradiation and cadmium (Cd) exposures on osteoblasts were observed in the present study. Osteoblasts were exposed to γ-irradiation (0.5 Gy) and Cd (0-0.5 μmol/L). Cell viability, alkaline phosphatase (ALP) activity, mineralization ability, cell apoptosis and genes expression of ALP, osteocalcin (OC) and caspase 3 were observed. Low concentrations of Cd exposure had no obvious influence on cell viability, ALP activity and apoptosis. However, low levels of Cd exposure combined with γ-irradiation induced more toxic effects on osteoblasts than those treated with Cd or irradiation alone. High concentrations of Cd combined with irradiation exposure induced more significant inhibition in cell viability, ALP activity and mineralization ability than those exposed to Cd or irradiation alone. Meanwhile, OC and ALP mRNA expression of cells treated with Cd combined with irradiation were down-regulated more significantly than those treated with Cd or irradiation alone. Cd combined with γ-irradiation could obviously enhance osteoblast apoptosis and up-regulated caspase 3 mRNA expression compared with those treated with Cd or irradiation alone. This study indicated that ionizing irradiation can enhance Cd toxic effects on osteoblast viability and differentiation and apoptosis may play an important role in this progress.     

Effects of the plant flavonoids silymarin and quercetin on arsenite-induced oxidative stress in CHO-K1 cells.

Chronic toxic effects of arsenic resulting from drinking water are a human health problem, especially in South-America and Asia. Arsenic is capable of influencing various cellular processes, causing adverse effects, including cancer. Although the exact mechanism of the action is not known, a correlation between oxidative stress, tumour promotion and arsenic exposure has been observed. We examined the effects of silymarin and quercetin, in counteracting oxidative stress produced by acute or sub-chronic sodium arsenite exposure. The stress responses to arsenite included an increase in the heat shock protein 70 kDa expression, lipid peroxidation assayed by conjugated dienes measure, and gamma-glutamyl-transpeptidase activity. We found that all these stress responses were eliminated by silymarin and quercetin in acute experiments. Both flavonoids diminished the conjugated dienes formation during sub-chronic cultures. Our results suggest that these antioxidant flavonoids, which may be easily incorporated into the diet, may afford a protective effect against arsenite-induced cytotoxicity.     

Cadmium-induced hepatic and renal injury in chronically exposed rats: likely role of hepatic cadmium-metallothionein in nephrotoxicity

Rats were injected sc with 0.5 mg Cd/kg, 6 days/week, for up to 26 weeks. Hepatic and renal function and tissue Cd and metallothionein (MT) content were determined in tissues and plasma at various times after Cd injection. Cd in liver and kidney increased linearly for the first 10 weeks of treatment, but thereafter hepatic concentrations of Cd decreased by 33% whereas the content of Cd in kidney remained constant. MT in liver and kidney increased linearly during the first 12 weeks of Cd treatment to 4400 and 2300 micrograms MT/g, respectively, but rose only slightly thereafter. Circulating concentrations of MT progressively increased beginning 2 weeks after Cd treatment and were approximately 10 times control values in rats dosed with Cd for 12 or more weeks. Plasma activities of alanine and aspartate aminotransferase exhibited a time course similar to that observed with MT, and were elevated as early as the sixth week of Cd exposure. Sharp increases in activities of these enzymes also occurred after 10 to 12 weeks of dosing. Hepatic microsomal metabolism of benzo[a]pyrene and ethylmorphine was severely attenuated beginning 4 weeks after Cd. Renal injury occurred after hepatic damage, as evidenced by decreased in vitro p-aminohippuric acid uptake beginning 8 weeks after exposure. Urine outflow increased threefold 11 weeks after Cd exposure began, while urinary protein and Cd excretion increased beginning at Week 9. These data indicate the liver is a major target organ of chronic Cd poisoning, and suggest that Cd-induced hepatic injury, via release of Cd-MT, may play an important role in the nephrotoxicity observed in response to long-term exposure to Cd.     

Influence of combined treatment with zinc and selenium on cadmium induced testicular pathophysiology in rat

The present study was conducted to evaluate the potential benefit of combined treatment with zinc (Zn) and selenium (Se) in reversing cadmium (Cd)-induced testicular pathophysiology compared to Se or Zn treatment alone in rats. For this purpose, male rats received either tap water, Cd, Cd + Zn, Cd + Se or Cd + Zn + Se in their drinking water, for 35 days. Cd exposure caused a significant decrease in plasma and testicular concentrations of Se and Zn which was accompanied by decreased plasma testosterone level, sperm count and motility, enzymatic activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) as well as by increased lipid peroxidation (as malondialdehyde, MDA). With Se or Zn administration, during exposure to Cd, only partial corrective effects on depletion of testicular and plasma Se and Zn levels, sperm characteristics and oxidative stress have been observed. The combined treatment of Cd-exposed animals with Se and Zn assured a more significant decrease in plasma and testicular Cd concentrations and a more efficient protection against the observed testicular damage as evidenced by the total prevention of both Se and Zn deprivation and by the entire restoration of the sperm motility and the testicular antioxidant status.     

Genetic variability in sublethal tolerance to mixtures of cadmium and zinc in clones of Daphnia magna Straus

To date, studies on genetic variability in the tolerance of aquatic biota to chemicals have focused on exposure to single chemicals. In the field, metals occur as elemental mixtures, and thus it is essential to study whether the genetic consequences of exposure to such mixtures differs from response to single chemicals. This study determined the feeding responses of three Daphnia magna Straus clones exposed to Cd and Zn, both individually and as mixtures. Tolerance to mixtures of Cd and Zn was expressed as the proportional feeding depression of D. magna to Cd at increasing zinc concentrations. A quantitative genetic analysis revealed that genotype and genotype x environmental factors governed population responses to mixtures of both metals. More specifically, genetic variation in tolerance to sublethal levels of Cd decreased at those Zn concentrations where there were no effects on feeding, and increased again at Zn concentrations that affected feeding. The existence of genotype x environmental interactions indicated that the genetic consequences of exposing D. magna to mixtures of Cd and Zn cannot be predicted from the animals' response to single metals alone. Therefore, current ecological risk assessment methodologies for predicting the effects of chemical mixtures may wish to incorporate the concept of genetic variability. Furthermore, exposure to low and moderate concentrations of Zn increased the sublethal tolerance to Cd. This induction of tolerance to Cd by Zn was also observed for D. magna fed algae pre-loaded with both metals. Furthermore, in only one clone, physiological acclimatization to zinc also induced tolerance to cadmium. These results suggest that the feeding responses of D. magna may be related to gut poisoning induced by the release of metals from algae under low pH conditions. In particular, both induction of metallothionein synthesis by Zn and competition between Zn and Cd ions for uptake at target sites on the gut wall may be involved in determining sublethal responses to mixtures of both metals.     

Endomorphin 1 effectively protects cadmium chloride-induced hepatic damage in mice

The antioxidative capacity of endomorphin 1 (EM1), an endogenous mu-opioid receptor agonist, has been demonstrated by in vivo assays. The present study reports the effect of EM1 on hepatic damage induced by cadmium chloride (Cd(II)) in adult male mouse. Mouse were given intraperitoneally (i.p.) a single dose of Cd(II) (1mg/kg body weight per day) and the animals were co-administrated with a dose of EM1 (50muM/kg body weight per day) for 6 days. Since hepatic damage induced by Cd(II) is related to oxidative stress, lipid peroxidation (LPO), protein carbonyl (PCO), superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH) were evaluated. The parameter indicating tissue damage such as liver histopathology was also determined. In addition, the concentrations of Cd and zinc (Zn) in the liver were analyzed. The intoxication of Cd(II) lead to the enhanced production of LPO and PCO, treatment with EM1 can effectively ameliorate the increase of LPO and PCO compared to the Cd(II) group. The increased activities of CAT, SOD and the elevated GSH induced by Cd(II) may relate to an adaptive-response to the oxidative damage, the effect of EM1 can restore the elevated antioxidant defense. Our results suggested that the structure features and the ability of chelating metal of EM1 may play a major role in the antioxidant effect of EM1 in vivo and opioid receptors may be involved in the protection of hepatic damage induced by Cd(II).     

Environmental exposure of the general population to cadmium as a risk factor of the damage to the nervous system: A critical review of current data

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.     

Distribution of cadmium chloride and cadmium-metallothionein to liver parenchymal, Kupffer, and endothelial cells: their relative ability to express metallothionein.

Acute exposure to cadmium (Cd) salts results in liver toxicity, while administration of cadmium-metallothionein (CdMT) iv, causes renal damage. When CdMT is administered iv there is a rapid accumulation of Cd in the proximal tubule cells of the kidney. In comparison, only small amounts of Cd accumulate in the liver following administration of CdMT. Thus, in order to better understand the regulation of MT as well as the toxicity of Cd, the present study has examined the ability of each of the three primary liver cells, parenchymal (PC), Kupffer (KC), and endothelial (EC), to accrue Cd after administration of either inorganic or organic forms of Cd. In addition, the relative ability of each cell type to express metallothionein (MT) mRNA and protein was examined. Following CdCl2 (3.5 mg Cd/kg) treatment, Cd concentrations increased to about the same degree in PC and KC, but EC had about 2-fold more than PC. After administration of CdCl2 (1.0 mg Cd/kg) each cell responded to the presence of Cd by increasing intracellular MT mRNA and protein. However, PC showed the greatest response, with a 30-fold increase in mRNA and a 21-fold increase in protein. Interestingly, KC and EC possessed intracellular Cd concentrations equal to or greater than that of PC, but contained less MT than would have been expected on the basis of their intracellular Cd concentrations. Thus, KC had a 7-fold increase in MT mRNA and a 2-fold increase in protein, while EC increased mRNA 3-fold and protein 2-fold over control values. In contrast, following CdMT (0.5 mg Cd/kg) administration, only low levels of Cd were detected, with similar concentrations in each cell type. After administration of CdMT (0.4 mg Cd/kg), PC again showed the greatest response, with a 3-fold increase in mRNA and a 6-fold increase in MT protein. Only slight changes were observed in KC and EC. In conclusion, the present study has shown the following: (1) Endogenous levels of MT in KC and EC are higher than those in PC. (2) Cd is readily accumulated by all three cell types, when administered as CdCl2, but not when given as CdMT. (3) PC, KC, and EC are capable of responding to intracellular Cd by increasing MT.