Reversal of Cadmium-Induced Thyroid Dysfunction by Selenium, Zinc, or Their Combination in Rat

The aim of this study was to evaluate the potential benefit of combined treatment with zinc (Zn) and selenium (Se) in reversing cadmium (Cd)-induced thyroid dysfunction compared to Se or Zn treatment alone in rats exposed to Cd. For this purpose, 30 adult male Wistar albino rats were equally divided into control and four treated groups receiving either 200 ppm Cd (as CdCl2), 200 ppm Cd + 500 ppm Zn (as ZnCl2), 200 ppm Cd + 0.1 ppm Se (as Na2SeO3), or 200 ppm Cd + 500 ppm Zn + 0.1 ppm Se in their drinking water for 35 days. The results showed that Cd exposure increased significantly the relative thyroid weight (RTW), the thyroid Cd concentration, and the serum thyroid stimulating hormone (TSH) level, whereas the serum thyroxine (T4) level was decreased compared to control rats. The treatment of Cd-exposed rats with Se alone only partially protected from the Cd-induced decrease in serum T4 level. The treatment of Cd-exposed animals with Zn alone partially protected against Cd-induced thyroid dysfunction by maintaining normal RTW and by decreasing Cd concentration in the thyroid. It also partially prevents Cd-induced decrease in serum T4 level. The combined treatment of Cd-exposed animals with Se and Zn induced a more significant decrease in the thyroid Cd concentration than the Zn supplement and a total correction of the RTW. This treatment was also more effective than that with Se or Zn alone in reversing Cd-induced decrease in serum T4 level and Cd-induced increase in serum TSH level. Se and Zn can have a synergistic role against Cd-induced thyroid dysfunction.     

Testicular toxicity induced by dietary cadmium is associated with decreased testicular zinc and increased hepatic and renal metallothionein and zinc in the bank vole <Emphasis Type="Italic">(Clethrionomys glareolus)</Emphasis>

Mechanism of testicular toxicity induced by dietary cadmium (Cd) has been less investigated than that following acute Cd injection. In the present study we characterized testicular injury in a small rodent, the bank vole, exposed subchronically to dietary Cd in a quantity of 0.9 mol/g, and determined the importance of some factors (Cd accumulation, metallothionein (MT), oxidative stress, and zinc (Zn)) in the injury. Dietary Cd induced moderate histopathological changes (hemorrhage in interstitium, necrosis and apoptosis in seminiferous tubule epithelium) in young (1 month old) bank voles fed, for 6 weeks, Fe-adequate (1.1–1.4 mol/g) and Fe-enriched (4.5–4.8 mol/g) diets. In contrast, adult (5 months old) bank voles appeared to be resistant to the toxic effects of dietary Cd, despite the fact that testicular Cd contents were higher and MT levels lower than those in the young animals. The Cd-induced histopathological changes and apoptosis were accompanied by increased testicular lipid peroxidation, decreased testicular Zn concentration and elevated levels of hepatic and renal MT and Zn. Supplemental dietary Zn (1.7–1.8 mol/g) prevented the Cd-induced testicular Zn depletion and injury. The data indicate that dietary Cd produces testicular lesions indirectly, through decreasing testicular Zn, which seems to be due to the sequestration of this element by the Cd-induced hepatic and renal MT.     

Formation of a double salt of phosphatidylcholine and zinc chloride.

ZnCl2 forms a 1 : 1 double salt with phosphatidylcholine. This compound resembles the long-known double salt of CdCl2 and phosphatidylcholine except that the latter has the composition (CdCl2)3(phosphatidylcholine)2. Treatment of phosphatidylcholine with a mixture of equimolar amounts of ZnCl2 and CdCl2 yields the ZnCl2 double salt. The ZnCl2 double salt can be obtained as an amorphous flocculent precipitate and as small spherules. These results are discussed in relation to the toxic action of cadmium salts on the mammalian testis and to the protection afforded by zinc salts. It is suggested that membrane phospholipids are essential components of specific sites for reversible binding of Zn2+ and Cd2+.     

Effects of prolonged oral administration of fumonisin B1 and aflatoxin B1 in rats

The effects of prolonged oral administration (21 days) of fumonisin B₁ (FB₁) and aflatoxin B₁ (AFB₁) were evaluated on male Wistar rats. The animals were housed in individual metabolic cages and submitted to the following treatments: 1-0 g AFB₁ + 0 mg FB₁/100g bw.; 2-72 g AFB₁+ 0 mg FB₁/100 g bw; 3-0 g AFB₁ + 0.5 mg FB₁ g bw; 4-0 g AFB₁ + 1.5 mg FB₁/100 g bw; 5-72 g AFB₁ + 0.5 mg FB₁/100g bw; 6-72 gAFB₁ + 1.5 mg FB₁/100g bw. On day 21, the rats were sacrificed for evaluation. The results showed that treated animals presented differences in body weight and absolute/relative weights of liver and kidney as well as altered hepatic function and cholesterol blood levels. Rats fed with the greatest doses of AFB₁ and FB₁ gained less weight (2.79 g/day) at the end of the experimental period; their blood concentrations of liver enzymes aspartate aminotransferase (AST) and alkaline phosphatase (AP) were above control levels (130.35 /l and 471.00 /l, respectively). Blood cholesterol increased in the groups treated with the highest dose ofFB₁ or FB₁ associated with AFB₁. Histopathology revealed the occurrence of apoptosis in the liver of rats exposed to FB₁. The association of aflatoxin B₁ with fumonisin B₁ at higher dose probably potentiated the effects of the higher dose of fumonisin B₁acting singly.This revised version was published online in October 2005 with corrections to the Cover Date.     

Effects of cadmium chloride on ovulation and on induction of sterility in the female golden hamster

The effects of single subcutaneous injections of cadmium chloride (CdCl2) on ovulation, egg transport and early pregnancy in the golden hamster were studied. While a single dose of 1.25 or 2.5 mg/kg of CdCl2 imposed none to marginal effects, hamsters treated with 5 or 10 mg/kg CdCl2 experienced a period of sterility ranging from 11-69 (5 mg/kg) or 46-71 (10 mg/kg) days, followed by a normal pregnancy. Administration of CdCl2 also induced ovulation inhibition which was dose-and time-dependent. A minimum dose of 5 mg/kg CdCl2 was needed to inhibit ovulation. When CdCl2 was given closer to the time of the luteinizing hormone (LH) surge on the day of proestrus, a more pronounced effect on ovulation was recorded. The incidence of failure of ovulation was associated with decreased progesterone levels in serum and inflammation, hemorrhages and necrosis in the ovary. However, the ovarian lesions lasted less than 4 days. The results indicate that CdCl2 inhibits ovulation when administered close to the time of ovulation, whereas its influence on pregnancy is pronounced but temporary.     

Role of alpha-tocopherol in cadmium-induced oxidative stress in Wistar rat's blood, liver and brain

Cadmium (Cd) a highly toxic metal is considered to be a multitarget toxicant, and it accumulates principally in the liver and kidney after absorption. In vivo studies of mouse and rat liver have shown that apoptosis plays a primary role in Cd-induced hepatotoxicity. However, the detailed mechanisms by which toxic metals such as Cd produce their effects are still largely unknown. The present study aimed at investigating the consequences of exposure to Cd, alpha-tocopherol and their combination on stress biochemical parameters (lipoperoxidation and protein carbonyls levels). Male albino Wistar rats (1 month old) were treated intravenously with cadmium (2 mg CdCl(2)/kg body weight/day), and alpha-tocopherol (100 mg/kg body weight/day), or with alpha-tocopherol+Cd (100 mg Vit E/kg body weight, 2 mg CdCl(2)/kg). The lipoperoxidation was measured by the thiobarbituric acid reactive substances (TBARS) method and oxidatively generated damage to proteins by determining carbonyl (DNPH) levels. Among the hematological parameters measured the haematocrit value and haemoglobin concentration were significantly decreased in the blood of Cd-treated rats. A significant increase was observed in the level of malondialdehyde (MDA) and protein carbonyls in the cadmium exposed group compared to control group (p<0.001), and these values were decreased after administration of alpha-tocopherol (group 4). The activity of lactate dehydrogenase in rat liver and brain showed a significant increase as compared to that found in the control group and significant decrease of catalase and superoxide dismutase activities. In the liver of the Cd-treated group the contents of reduced glutathione were decreased. Our results suggest that cadmium induces an oxidation of cellular lipids and proteins and that administration of alpha-tocopherol can reduce Cd-induced oxidative stress and improve the glutathione level together with other biochemical parameters.     

Protective effect of zinc supplementation on blood antioxidant defense system in rats exposed to cadmium

The aim of this study was to assess the effects of subchronic exposure to cadmium (Cd) on the antioxidant defense system of red blood cells (RBCs) and lipid peroxide concentration in the plasma, as well as the possible protective role of zinc (Zn). For this purpose, 60 male Wistar rats (8 weeks old) were divided into three groups: the first group was exposed to Cd in the form of CdCl₂, administered in five doses (each of 0.4 mg Cd/kg BW) on days 5, 10, 15, 20 and 25, giving a total dose of 2 mg Cd/kg BW, i.p.; the second group was simultaneously exposed to Zn and Cd with the same timeline and the same doses of Cd as the first group but with, in addition, injections of Zn in the form of ZnCl₂, administered in doses of 0.8 mg Zn/kg BW, giving a total dose of 4 mg Zn/kg BW, i.p.; a control group received 0.5 mL of physiological saline in an identical manner.

It was shown that exposure to Cd induced a significant decrease (p<0.05) in superoxide dismutase (Zn/Cu SOD) and catalase (CAT) activities in RBCs. Increased lipid peroxide concentration, measured by thiobarbituric acid reactive substances (TBARS), was also observed in the plasma of cadmium-exposed rats. Cd had no effect on glutathione peroxidase (GSH-Px) activity. Zn administration had a beneficial effect on the Cd-induced decrease in Zn/Cu SOD activity (p<0.05) but not on CAT activity. Animals receiving Cd and Zn simultaneously had significantly (p<0.05) lower concentrations of lipid peroxides than rats exposed to Cd alone. Our results indicate that Cd causes oxidative stress and that Zn supply in conditions of exposure to Cd can partially protect against Cd-induced oxidative stress.     

Dithiocarbamates and prevention of cadmium teratogenesis in the hamster

Certain dithiocarbamates (DTC) have been reported to protect against cadmium (Cd)-induced lethality and to decrease Cd body burden. The present study evaluated the influence of sodium N-benzyl-D-glucamine dithiocarbamate, sodium N-di(hydroxyethyl)amine dithiocarbamate, sodium 4-carboxyamidopiperidine-N-dithiocarbamate, and sodium N-methyl-D-glucamine dithiocarbamate on Cd-induced teratogenesis in the hamster. When given as a single ip injection at 2.2 mmol/kg 15 min prior to iv CdCl2 (2 mg/kg), all of the DTC afforded significant protection against Cd-induced developmental toxicity and reduced kidney [Cd] in the dam. Maternal liver [Cd] was reduced with the glucamine and dihydroxyethyl amine analogs, but treatment with the piperidine failed to influence hepatic [Cd]. Pretreatment of the dams with DTC 24 hr prior to Cd challenge failed to protect against Cd-induced embryotoxicity, and provided minimal, if any, reduction in renal or hepatic [Cd]. Pretreatment with the N-methyl-D-glucamine congener 24 hr prior to Cd exposure increased embryolethality. The dose-time relationships found here suggest that pharmacologically effective levels of these DTC decline within 24 hr of treatment and that induction of metallothionein does not play a major role in DTC antagonism of Cd poisoning.     

Turnover of metallothioneins in rat liver.

Two electrophoretically distinguishable metallothioneins were isolated from the livers of Cd2+-treated rats and had thiol group/metal ratios of 3:1, a total metal content, in each of these proteins, of 3.6 atoms of Cd2+ + 2.4 atoms of Zn2+/molecule and 4.2 atoms of Cd2+ + 2.8 atoms of Zn2+/molecule and respective apoprotein mol.wts. of 5844 and 6251. Studies with 1 h pulse labels of [3H]cysteine, given after a single injection of ZnCl2 or CdCl2, showed that these metals stimulated radioactive isotope incorporation into the metallothioneins over the control value by 10- and 15-fold respectively. This stimulation was maximal at 4 h after a single CdCl2 injection and decreased to control values by 16 h, suggesting that either a translational event is responding to free intracellular Cd2+ or a short-lived mRNA is being produced or stabilized in response to the metal treatment. In rats chronically exposed to CdCl2, the metallothioneins increased to 0.2% of the liver wet weight from a control value of 2--4 mumol/kg of liver, with a maximum rate of accumulation of 2--3 mumol/h per kg of liver. The turnover of these proteins in control animals was 0.3--0.6 mumoles/h per kg of liver, measured by the rate of disappearance of 203Hg2+, which binds irreversibly to the metallothioneins. Pretreatment with CdCl2 completely stopped the rapid 203Hg turnover observed in untreated animals. Unlike CdCl2, treatment with ZnCl2 increased the concentration of metallothioneins to a new steady-state pool, 11 mumole/kg of liver, after 10 h. The increase in the zinc-thionein pool by exposure to ZnCl2 in vivo was determined to be primarily due to a stimulation of metallothionein biosynthesis.     

Long-term effects of a single cadmium chloride injection on the ovulation, ovarian progesterone and estradiol-17 beta secretion in rats

On the day of dioestrus II rats were given 5, 10 or 15 mg/kg of cadmium chloride (CdCl2), or 1, 0 ml/kg of 0.9% NaCl solution. Then ovarian cycle was checked daily for a period of 12 cycle length. On the day of oestrus or expected oestrus in the 13th cycle the animals were anaesthetized with pentobarbital and cannulas were inserted in one of the femoral arteries and veins and in one of the utero-ovarian veins. Five-minute blood fractions were collected for 40 minutes and following the first blood samples 10 IU of hCG were injected iv. Ovarian venous outflow and blood pressure were continuously recorded. From the blood fractions progesterone (P) and oestradiol-17 beta (E2) were determined with RIA and the P and E2 secretion rates of ovary were calculated. Ovaries were excised and oviducts were flushed for counting oocytes. CdCl2 shortly after its administration induced a (dose-dependent) anoestrous period which turned into regular or irregular cycles depending on the dose. Part (28-32%) of the oestrous animals (14% that of the controls) remained unovulatory, when ovulation occurred normal number of ova was found. None of the doses of CdCl2 has influenced the blood pressure of animals and blood flow of the ovary. The basal secretion rate of P and E2 was not changed in the ovary compared to the controls. The hCG induced rise of P secretion, however, in the animals treated with 5 and 10 mg/kg bw CdCl2 was diminished and delayed, while in the animals treated with the 15 mg/kg Cd dose a complete lack of response was observed.     

The interaction of cadmium-binding proteins (Cd-bp) and progesterone in cadmium-induced tissue and embryo toxicity.

Previous work indicates that a dimer of Cd-thionein (Cd-bp-D, 19,000 MW) is involved in the hereditary resistance to Cd-embryotoxicity seen in the inbred NAW/Pr (NAW) mouse strain. Cd-bp-D is not detected in virgin females after Cd exposure and is detected only after the first 24 hours of exposure to Cd in an inbred strain (C57BL/10ChPr) susceptible to Cd-induced embryotoxicity (Wolkowski, '74; Wolkowski-Tyl, '78). Since progesterone (P) is critical for maintenance of pregnancy in mice, we have studied the possible relationship between this hormone and Cd-bp-D production. As a model system, was examined effects of Cd treatment on Cd-bp synthesis in NAW males. It was anticipated that this model could provide information bearing not only on the relationship between P and Cd-bp-D production, but also on that between Cd-bp-D and Cd toxicity, since a single sc injection of CdCl2 causes typical testicular hemorrhagic necrosis in NAW males, and these animals make only metallothionein and not Cd-bp-D. NAW males were, therefore, given P (0.1 g/Kg bw) and then exposed to Cd. Sephadex gel chromatography (G-200) of liver cytosol from animals killed 24 hours later detected only Cd-bp-D. Testes of these males did not show hemorrhagic necrosis. Since the adrenals of male mammals release P in response to stress, NAW males were stressed by repeated sesame oil or propylene glycol injections (5 ml/Kg bw), or the adrenal was stimulated directly with injections of ACTH (100 IU/Kg bw) for seven days prior to Cd exposure. All methods tested which significantly elevated serum P levels (as confirmed by radioimmunoassay), also resulted in production of Cd-bp-D and absence of testicular hemorrhage in Cd-treated NAW males. Suppression of P release by injection of dexamethazone or corticosterone or by adrenalectomy resulted in testicular hemorrhage and production of only metalicthionein after Cd exposure. The relevance of the interaction between P, Cd-bp-D and protection against Cd-induced toxicity seen in the model system was supported by analysis of serum P levels in pregnant females; elevated levels were seen in resistant (NAW dams on day 10 of gestation and significantly lower levels seen in dams from a Cd-sensitive strain.     

Effects of Cd and Zn on the development of annual xylem rings of young Norway spruce (Picea abies) plants

Three-year-old spruce (Picea abies) saplings were planted and cultivated for 2 years in pots with 3 1 substrate, consisting of a homogenized mixture of sand, peat and forest soil with a high organic content (volume ratio 11.52). This substrate was amended with 10–180 mol Cd [kg soil dry weight (DW)]^–1, 50–7500 mol Zn (kg soil DW)^–1 (determined with 1 M ammonium acetate extracts) or combinations of both elements. Annual xylem growth rings in stems of plants treated with 50 mol Cd (kg soil DW)^–1 or 7500 mol Zn (kg soil DW)^–1 were significantly narrower than in control plants. Growth reductions were more pronounced in the second year of the experiment. The contents of Cd and Zn in stem wood and needles were positively correlated with the substrate concentrations. The Mg contents of the spruce needles were inversely correlated with soil concentrations of Cd and Zn. Root development was impeded at moderate concentrations of Cd (50 mol kg^–1) or Zn (1000 mol kg^–1) in the substrate. The adverse effects of potentially toxic trace elements, like Cd or Zn, on xylem growth of spruce plants are discussed with regard to possible growth reductions in forest trees under field conditions.     

Hepatoprotective Potentials of Onion and Garlic Extracts on Cadmium-Induced Oxidative Damage in Rats

The hepatoprotective effect of onion and garlic extracts on cadmium (Cd)-induced oxidative damage in rats is reported. Control group received double-distilled water alone. Cd group was challenged with 3CdSO₄·8H₂O (as Cd; 1.5 mg/kg bw per day per oral) alone, while extract-treated groups were pretreated with varied doses of onion and/or garlic extract (0.5 and 1.0 ml/100 g bw per day per oral) for a week and thereafter co-treated with Cd (1.5 mg/kg bw per day per oral) for 3 weeks. Cd caused a marked (p?<?0.001) increase in the levels of lipid peroxidation and glutathione S-transferase, whereas glutathione, superoxide dismutase, and catalase levels were decreased in the liver. We also observed a decrease in hepatic activities of alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase and a concomitant increase in the plasma activities of ALT and AST. Onion and garlic extracts significantly attenuated these adverse effects of Cd. Onion extract proffered a dose-dependent hepatoprotection. Our study showed that Cd-induced oxidative damage in rat liver is amenable to attenuation by high dose of onion and moderate dose of garlic extracts possibly via reduced lipid peroxidation and enhanced antioxidant defense system that is insufficient to prevent and protect Cd-induced hepatotoxicity.     

Influence of UV-B radiation and Cd2+ on chlorophyll fluorescence, growth and nutrient content in Brassica napus

The possible interaction of two stresses, UV-B radiation and cadmium, applied simultaneously, was investigated in Brassica napus L. cv. Paroll with respect of chlorophyll fluorescence, growth and uptake of selected elements. Plants were grown in nutrient solution containing CdCl2, (0, 0.5, 2 or 5 M) and irradiated with photosynthetically active radiation (PAR, 400-700 nm, 800 mol m^-2 s^-1) with or without supplemental ultraviolet-B radiation (UV-B, 280-320 nm, 15 kJ m^-2 d^-1, weighted irradiance). After 14 d of treatment, the most pronounced effects were found at 2 and 5 M CdCl2 with and without supplemental UV-B radiation. Exposure to cadmium significantly increased the amount of Cd in both roots and shoots. In addition, increases occurred in the concentrations of Fe, Zn, Cu, and P in roots, while K was reduced. In shoots the S content rose significantly both in the presence and absence of UV-B radiation, while significant increases in Mg, Ca, P, Cu, and K occurred only in plants exposed to Cd and UV-B radiation. Manganese decreased significantly under the combined exposure treatment. The rise in S content may have been due to stimulated glutathione and phytochelatin synthesis. Cadmium exposure significantly decreased root dry weight, leaf area, total chlorophyll content, carotenoid content, and the photochemical quantum yield of photosynthesis. As an estimation of energy dissipation processes in photosynthesis, non-photochemical quenching (qNPQ) was measured using a pulse amplitude modulated fluorometer. The qNPQ increased with increasing Cd, while the combination of cadmium and UV-B reduced the qNPQ compared to that in plants exposed only to cadmium or UV-B radiation. The chlorophyll a:b ratio showed a reduction with UV-B at no or low Cd concentrations (0 M, 0.5 M CdCl2), but not at the higher Cd concentrations used (2 M, 5 M CdCl2). Thus in some instances there appeared to be a UV-B and Cd interaction, while in other plants response could be attributed to either treatment alone.Keywords: Brassica napus, cadmium, ultraviolet-B radiation.      

Cadmium-induced ovarian pathophysiology is mediated by change in gene expression pattern of zinc transporters in zebrafish (Danio rerio)

This study explored the potential for expression pattern of genes encoding zinc (Zn) transporters to be involved in the cadmium (Cd)-induced reproductive toxicity in female of zebrafish. For this purpose, oocytes maturity and ovarian histology as well as Cd, Zn and metallothioneins (MTs) accumulation and expression of genes encoding Zrt-,Irt-related protein 10 (ZIP10), Zn transporter 1 (ZnT1) and zebrafish metallothionein (zMT) were examined in ovaries of adult zebrafish exposed to 0.4 mg/L Cd in water and supplemented with Zn (5 mg kg⁻¹) in their diet for 21 days. Cd-exposure decreased the expression of ZnT1 and caused up-regulation of ZIP10 and zMT gene expression. These changes were accompanied by increased Cd and MTs accumulation, decreased Zn contents as well as by histopathological damages in ovarian tissues. The co-exposure of fish to Cd and Zn abolished ZnT1 down-regulation and rendered a persistently increased ZIP10 mRNA level. This treatment also decreased Cd and MTs accumulation, reversed Cd-induced Zn depletion and partially restored Cd-induced histological changes in ovarian tissues. These results imply that the downregulation of ZnT1 as well as the overexpression of ZIP10, in responses to the ovarian Zn depletion induced by Cd, play a major role in Cd accumulation and consequently in its toxicity. The protective effect of dietary Zn supplementation against Cd-induced toxicity is mediated, at least in part, by the increase of Zn availability and subsequently the induction of ZnT1 gene expression.     

Tissue susceptibility factors in cadmium carcinogenesis

Recently, in two separate studies we have observed cadmium (Cd)-induction of prostatic tumors (PT) in rats. Cd (sc or im) at doses nontoxic to the testes markedly increased PT formation (2.5 μmol/kg, sc, 8 PT/29 exposed, 28%; 30 μmol/kg, im, 11/26, 42%; control 14/127, 11%). The administration of zinc (Zn; 1 mmol/kg, sc, at ?6, 0 and +18 h) to prevent testicular toxicity and tumors from Cd (30 μmol/kg, sc, 0 h) also resulted in an elevated incidence of PT (8/27, 30%). The nature of the metal-binding proteins in the prostate has not been defined, although metallothionein (MT), a low M_r Cd-binding protein that confers tolerance to Cd, is deficient in other target tissues of Cd carcinogenesis, such as the rat testes. Using a technique that extracts MT from liver, a low-M_r Cd-binding protein was extracted from both ventral (VP) and dorsal prostate (DP) and isolated by gel filtration. In contrast to the two forms of rat MT, reverse phase HPLC of VP and DP extract eluted 1 and 5 forms, respectively. The amino acid compositions of the VP and DP proteins were quite distinct from MT, with much less cys than MT and the presence of residues not found in MT (leu, tyr, phe). Thus Cd-induction of PT appears to be dependent on functional testes and, as is the case with Cd-induced testicular formation, appears to be associated with a deficiency of MT.     

Metallothionein in the liver of the small lizard Podarcis muralis

A cysteine-rich protein presenting optical and biochemical features typical of metallothionein and a similar amino acid composition was found in the liver of the small lizard Podarcis muralis. Animals were given either CdCl2 (0.8 mg Cd2+/kg body wt) or saline (NaCl 0.9%) by i.p. injection for 3 days. A second group of animals were injected with a single dose of [35S]cysteine plus CdCl2 or saline. Lizard MT contained Zn and Cu when injected with saline and also Cd when injected with CdCl2. Metallothionein induction by cadmium was demonstrated by radioactive labelling.     

Role of beta-carotene in ameliorating the cadmium-induced oxidative stress in rat brain and testis

The role of oxidative stress in chronic cadmium (Cd) toxicity and its prevention by cotreatment with beta-carotene was investigated. Adult male rats were intragastrically administered 2 mg CdCl2/kg body weight three times a week intragastrically for 3 and 6 weeks. Brain and testicular thiobarbituric acid reactive substances (TBARS) was elevated after 3 and 6 weeks of Cd administration, indicating increased lipid peroxidation (LPO) and oxidative stress. Cellular damage was indicated by inhibition of adenosine triphosphatase (ATPase) activity and increased lactate dehydrogenase (LDH) activity in brain and testicular tissues. Chronic Cd administration resulted in a decline in glutathione (GSH) content and a decrease of superoxide dismutase (SOD) and glutathione S-transferase (GST) activity in both organs. Administration of beta-carotene (250 IU/kg i.g.) concurrent with Cd ameliorated Cd-induced LPO. The brain and testicular antioxidants, SOD, GST, and GSH, decreased by Cd alone, were restored by beta-carotene cotreatment. Concurrent treatment with beta-carotene also ameliorated the decrease in ATPase activity and the increase in LDH activity in brain and testis of Cd-treated rats, indicating a prophylactic action of beta-carotene on Cd toxicity. Therefore, the results indicate that the nutritional antioxidant beta-carotene ameliorated oxidative stress and the loss of cellular antioxidants and suggest that beta-carotene may control Cd-induced brain and testicular toxicity.     

Distribution of cadmium in ovaries, adrenals and pituitary gland after chronic administration in rats.

Wistar rats were given 0.25, 0.5 or 1.0 mg/kg/week CdCl2 for 14, 18 or 22 weeks and the body weight, Cd content of ovaries, adrenals, pituitary gland, furthermore the progesterone and oestradiol-17 beta secretion of ovary were checked. Cd treatment caused a slight decrease in the body weight, but failed to alter the weight of endocrine organs. CdCl2 in a dose of 0.25 mg/kg/week resulted in almost the same Cd content in all the three organs. Rising the amount of Cd administered the pituitary gland accumulated more Cd than the adrenals, and the lowest levels were found in the ovary. CdCl2 even in the dose of 1.0 mg/kg/week failed to alter the ovarian cycle, progesterone and oestradiol-17 beta production of ovary. The data point also to a developing tolerance to Cd as the cumulative dose of CdCl2 lies close to the LD50 levels.