[Effect of phosphor on accumulation and chemical forms of cadmium, and physiological characterization in different varieties of Capsicum annuum L].

Pot experiments were carried out to investigate the influence of different Phosphor (P) levels (0, 0.3% and 0.5%) on the plant growth, activities of antioxidant enzymes, accumulation and chemical forms of cadmium (Cd) in Capsicum annuum L. when exposed to Cd (10 mg x kg(-1)). The results showed that dry weights of leaf, fruit, roots and total dry weights of plant, and concentration and accumulation of Cd significantly differed between two varieties of Capsicum annuum L. Dry weights of fruit and total plant of Chaotianjiao increased by P (0.3% and 0.5%), while that of Yanjiao425 was inhibited. Activities of catalase (CAT) were increased at first, and then reduced in the presence of P; Activities of superoxide dismutase (SOD) and peroxidase (POD) of Chaotianjiao increased with increasing levels of P, but activities of SOD and POD of Yanjiao425 decreased with increasing levels of P. Chemical forms of Cd in fruit of Capsicum annuum L. were in order of F(NaCl) > F(HAC) > F(E) > Fr > F(HC) > F(W). The total extractable Cd, ethanol-extractable Cd, hydrochloric acid-extractable Cd and residual Cd in fruit of Ynajiao425 obviously decreased in the presence of P compared to the control, while the total extractable Cd, water-extractable Cd, acetic acid-extractable Cd and residual Cd in fruit of Chaotianjiao increased. Cadmium accumulations of Capsicum annuum L. were in order of roots > stew > leaf > fruit. Cadmium accumulations in fruit and plant of Yanjiao425 were decreased by 47.7% and 58.5% , 5.5% and 13. 1% in the presence of 0.3% and 0.5% P when exposed to Cd, and Cd accumulations in fruit and plant of Chaotianjiao were decreased by 23.6% in the presence of 0.3% P.

The protective role of zinc and calcium in Vicia faba seedlings subjected to cadmium stress.

The aim of the present study was to evidence the possible antagonistic effect of Zinc (Zn(2+)) and Calcium (Ca(2+)) against cadmium (Cd(2+))-induced DNA damage by using random amplification of polymorphic DNA (RAPD) and metabolic activities in Vicia faba. The results showed that all doses of Cd(2+) (10( -3) M, 10(-5) M) caused an increase in polymorphism value and a decrease in genomic template stability (GTS %). In addition, when 10( -4)-10(-6) M Ca(2+), 10(-6) M Zn(2+) were added together with 10(-3) M, 10(-4) M, 10(-5) M of Cd(2+), polymorphism value decreased besides GTS, total protein and chlorophyll content increased. Results suggested that Zn(2+) and Ca(2+) have an antagonistic effect against Cd(2+). The order of the antagonisms of Ca(2+), Zn(2+) against Cd(2+) toxicity was Ca(2+) > Zn(2+). Especially, the degree of antagonistic effect of Zn(2+) against Cd(2+) is probably related to its concentration ratio.

[Effects of hydroxyapatite on growth and quality of potato (Solanum tuberosum L.) in Cd polluted soil].

A pot experiment was conducted in a glasshouse to study effects of hydroxyapatite amending Cd polluted soil on growth and quality of potato (Solanum tuberosum L.). In the experiment, 3 levels of Cd pollution (0, 5, and 10 mg x kg(-1)) and 6 levels of hydroxyapatite application (0, 4, 8, 10, 16, and 30 g x kg(-1)) in soil were prepared to plant 2 potato varieties (Zhongshusanhao and Daxiyang in Chinese system). The results showed that Cd pollution in soil resulted in decrease in yield per plant of potato; for example, in the soils with 5 and 10 mg x kg(-1) of Cd, the yield per plant decreased 24%-31% and 41%-45%, respectively. Applying hydroxyapatite to Cd pollution could greatly increase yield per plant of potato. Compared to the soil without hydroxyapatite, 10 or 30 g x kg(-1) hydroxyapatite added to the soil with 5 or 10 mg x kg(-1) of Cd increased 17%-9% or 45%-58% in yield per plant. Due to hydroxyapatite amending Cd polluted soil, chlorophyll contents in leaves and superoxide dismutase (SOD) activities in tubers enhanced and malondialdehyde (MDA) contents in tubers declined apparently. Meanwhile, quality of potato tubers was obviously improved, such as increase in vitamin C contents, starch contents, and protein contents in potato tubers. With hydroxyapatite applying from 0 to 30 g x kg(-1), Cd contents in potato tubers deceased from 0.87-0.95 mg x kg(-1) to 0.13-0.21 mg x kg(-1) by 78%-85% in the soils with 5 mg x kg(-1) of Cd, and from 1.86-1.93 mg x kg(-1) to 0.52-0.65 mg x kg(-1) by 66%-72% in the soils with 10 mg x kg(-1) of Cd. The experiment indicated that the mechanism of hydroxyapatite alleviating soil Cd toxicity main included rising soil pH values, reducing effective Cd contents in soil, and Ca from hydroxyapatite blocking soil Cd moving to potato. However, ability of hydroxyapatite alleviating soil Cd toxicity was limited, and excessive hydroxyapatite to soil exhibited stress effects on growth and quality of potato. In the Cd polluted soils with proper hydroxyapatite, growth and quality of Zhongshusanhao were better than those of Daxiyang, indicating different responses of various potato varieties to environment amelioration.

[Effect of different zinc levels on accumulation and chemical forms of cadmium, and physiological characterization in Capsicum annuum L].

Pot experiments were carried out to investigate the influence of different zinc (Zn) levels (0, 100, 200, 400 and 600 micromol x L(-1)) on the plant growth,activities of antioxidant enzymes, contents of chlorophyll a and b, accumulation and chemical forms of cadmium (Cd) in Capsicum annuum L. when exposed to Cd (20 mg x kg(-1)). The results showed that dry weights of leaf, stem, fruit and root, and contents of chlorophyll a and b in Capsicum annuum L. were increased by Zn ( < or = 400 micromol x L(-1)), while inhibited by high Zn (600 micromol x L(-1)). Activities of superoxide dismutase (SOD) and catalase (CAT) were reduced by Zn ( < or =400 micromol x L(-1)), the lowest activities of SOD and CAT were recorded in 400 micromol x L(-1) Zn, but activities of SOD and CAT were increased when Zn >400 micromol x L(-1). Cadmium concentrations in stem, fruit and root of Capsicum annuum L. were decreased by 2.7%-5.4%, 7.5%-28.1% and 7.6%-21.8% in the presence of Zn when exposed to Cd. The total extractable Cd, NaCl- extractable Cd, water-extractable Cd and ethanol-extractable Cd in fruit were reduced by 7.7%-21.8%, 4.11%-23.6%, 54.5%-66.8% and 4.8%-86.7% in the presence of Zn,while acetic acid- extractable Cd and residual Cd were increased by 28.0%-68.0% and 12.6%-25.0%.

Effects of chlorimuron-ethyl and cadimum on biomass growth and cadimum accumulation of wheat in the phaiozem area, Northeast China.

The joint effect of chlorimuron-ethyl and cadmium (Cd) on biomass growth and cadmium accumulation in wheat (Triticum aestivum L.) was investigated and compared with single-factor effect of soil cadmium pollution. The results showed that dry biomass of wheat had significantly (p < 0.01) negative relationships with increasing concentrations of chlorimuron-ethyl and cadmium in phaiozem. The highest inhibition rates observed were 76.2%, 62.7% and 55.6% for roots, shoots and glumes, respectively, when the concentration of cadmium in soil was up to 100 mg kg(-1). There were synergistically inhibitory interactions between chlorimuron-ethyl and cadmium on biomass growth of wheat. The SPT values of cadmium for wheat decreased with an increase in the concentration of cadmium added to the tested soil. The accumulation of cadmium in wheat shoots, roots and glumes could be inhibited by chlorimuron-ethyl to some extent. There was an antagonistic interaction between chlorimuron-ethyl and cadmium on accumulation of cadmium in wheat.

[Cilostazol induces metallothionein expression in vascular cells].

Metallothionein (MT) is a cysteine-rich low molecular weight protein and thought to function in the detoxification of heavy metals and reactive oxygen species. We examined the induction of MT synthesis by cilostazol, an antiplatelet drug, in several vascular component cells to find a new pharmacological effect of cilostazol in vascular system. In human coronary artery endothelial cells, cilostazol significantly increased MT-IX and MT-IIA mRNA levels after the treatment for 6 h and endogenous MT-I/II protein levels after the treatment for 24 and 48 h. In addition, cadmium cytotoxicity was prevented by cilostazol in this endothelial cells. Moreover, cilostazol increased MT-IX and MT-IIA mRNA levels in human coronary artery smooth muscle cells, human brain microvascular endothelial cells, human brain microvascular pericytes and human colon carcinoma Caco-2 cells after the treatment for 6 h. Interestingly, cilostazol also increased MT-III mRNA level in brain microvascular endothelial cells more effectively than in other vascular cells. The present results suggest that cilostazol can protect the vascular system from toxic substances such as heavy metals via MT induction in vascular cells.

Hwanggunchungyitang prevents cadmium-induced ototoxicity through suppression of the activation of caspase-9 and extracellular signal-related kinase in auditory HEI-OC1 cells.

Hwanggunchungyitang (HGCYT) is a newly designed herbal drug formula for the purpose of treating auditory diseases. A number of heavy metals have been associated with toxic effects to the peripheral or central auditory system. Cadmium (Cd(2+)) is a heavy metal and a potent carcinogen implicated in tumor development through occupational and environmental exposure. However, the auditory effect of Cd(2+) is not poorly understood. The purpose of the present study was to investigate whether HGCYT prevent the ototoxic effects induced by Cd(2+) in auditory cell line, HEI-OC1. HGCYT inhibited the cell death, reactive oxygen species generation (ROS), activation of caspase-9, and extracellular signal-related kinase (ERK) induced by Cd(2+). In addition, we observed that cochlear hair cells in middle turn were damaged by Cd(2+). However, HGCYT prevented the destruction of hair cell arrays of the rat primary organ of Corti explants in the presence of Cd(2+). These results support the notion that ROS are involved in Cd(2+) ototoxicity and suggest HGCYT therapeutic usefulness, against Cd(2+)-induced activation of caspase-9 and ERK.

Protective effects of selenium, zinc, or their combination on cadmium-induced oxidative stress in rat kidney.

The present study was conducted to investigate whether the combined treatment with Se and Zn offers more beneficial effects than that provided by either of them alone in reversing Cd-induced oxidative stress in the kidney of rat. For this purpose, 30 adult male Wistar albino rats, equally divided into control and four treated groups, received either 200 ppm Cd (as CdCl(2)), 200 ppm Cd + 500 ppm Zn (as ZnCl(2)), 200 ppm Cd + 0.1 ppm Se (as Na(2)SeO(3)), or 200 ppm Cd + 500 ppm Zn + 0.1 ppm Se in their drinking water for 35 days. The results showed that Cd treatment decreased significantly the catalase (CAT) and glutathione peroxidase (GSH-Px) activities, whereas the superoxide dismutase (SOD) activity and the renal levels of lipid peroxidation (as malondialdehyde, MDA) were increased compared to control rats. The treatment of Cd-exposed rats with Se alone had no significant effect on the Cd-induced increase in the MDA concentrations but increased significantly the CAT activities and reversed Cd-induced increase in SOD activity. It also partially prevented Cd-induced decrease in GSH-Px activity. The treatment of Cd-exposed animals with Zn alone increased significantly the CAT activity and partially protected against Cd-induced increase in the MDA concentrations, whereas it had no significant effect on the Cd-induced increase in SOD activity and decrease in GSH-Px activity. The combined treatment of Cd-exposed animals with Se and Zn was more effective than that with either of them alone in reversing Cd-induced decrease in CAT and GSH-Px activities and Cd-induced increase in MDA concentrations. Results demonstrated beneficial effects of combined Se and Zn treatment in Cd-induced oxidative stress in kidney and suggest that Se and Zn can have a synergistic role against Cd toxicity.

Protective roles of onion and garlic extracts on cadmium-induced changes in sperm characteristics and testicular oxidative damage in rats.

Cadmium (Cd) is known to exert gonadotoxic and spermiotoxic effects. The present study was performed to assess the possible protective roles of onion (Allium cepa Linn) and garlic (Allium sativum Linn) extracts on Cd-induced testicular damage and spermiotoxicity. The control group received double distilled water; Cd group received Cd (1.5mg/100g BW/day) orally; extract-treated groups were pre-treated with varied doses of onion and/or garlic extract (0.5ml and 1.0ml/100g BW/day) orally for one week and then simultaneously challenged with Cd (1.5mg/100g BW/day) for additional three weeks. Testicular tissue oxidant/antioxidant status and sperm characteristics were determined. Cd caused a marked (p<0.001) rise in testicular lipid peroxidation (LPO) and glutathione S-transferase (GST) levels whereas glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and alkaline phosphatase (ALP) levels were decreased. Cd intoxication significantly (p<0.001) decreased epididymal sperm concentration and sperm progress motility, increased percent total sperm abnormalities and live/dead count. Both extracts successfully attenuated these adverse effects of Cd. Onion extract offers a dose-dependent protection. Our study demonstrated that aqueous extracts of onion and garlic could proffer a measure of protection against Cd-induced testicular oxidative damage and spermiotoxicity by possibly reducing lipid peroxidation and increasing the antioxidant defence mechanism in rats.

Protective effects of selenium (Se) and zinc (Zn) on cadmium (Cd) toxicity in the liver and kidney of the rat: histology and Cd accumulation.

UNLABELLED: To assess the co-effect of Se and Zn on Cd accumulation in the liver and kidney and on their histology, male rats were exposed either to Cd, Cd+Zn, Cd+Se, or Cd+Zn+Se in their drinking water, during 35 days. Exposure to Cd resulted in its accumulation in the liver and kidney. In the Cd-Zn and Cd-Zn-Se groups, Cd contents in the two organs were significantly (p < 0.01) higher than those in the Cd group. Se did not induce any significant difference in hepatic and renal concentrations of Cd in comparison to Cd-treated group. Light microscopic examination indicated severe histological changes in the two organs under Cd influence. Se or Zn partially alleviated the damage observed in the liver. The same effect was remarked in the kidney with Se, but no differences in the renal histological structure have been observed between the Zn-Cd and the control groups. With Se and Zn simultaneous treatment during Cd exposure, the observed morphological changes had practically disappeared from the liver, but were only reduced in the kidney. CONCLUSION: Se and Zn can have a cooperative effect in the protection against Cd-induced structural damage in the liver but not in the kidney.

Prevention of cadmium accumulation in retinal pigment epithelium with manganese and zinc.

Age-related macular degeneration (AMD) is a leading cause of irreversible blindness in the elderly. Risk factors include old age, female gender, obesity, smoking, low dietary intakes of antioxidants and increased exposure to the toxic metal cadmium (Cd(2+)). Supplementation with high-dose zinc (80 mg) provides some protection, but the mechanism(s) underlying such protection has not been fully elucidated. The present study had a focus on the human retinal pigment epithelial (RPE) cell line ARPE-19 in an attempt to demonstrate a reduction in intracellular Cd(2+) effect associated with heme oxygenase-1 (HO-1) expression by co-exposure with zinc (Zn(2+)) or manganese (Mn(2+)), which is known to be a more potent inhibitor of Cd(2+) uptake than Zn(2+). Our results indicated that co-exposure of 10 microM Cd(2+) with 5 microM Mn(2+) reduced the intracellular Cd(2+) effect by 50-60%, possibly by limiting the amounts of Cd(2+) entering cells through Mn(2+) transporter protein (ZIP8). A similar reduction in a Cd(2+) effect was achieved by co-exposure with 20 microM Zn(2+) while co-exposure with 5 and 10 microM Zn(2+) ions was ineffective. Mn(2+) ions as low as 2.5 microM were found to cause an increase in HO-1 mRNA expression levels in ARPE-19 cells, demonstrating for the first time that Mn(2+) is an inducer of HO-1. Mn(2+) ions at 1 microM induced HO-1 mRNA expression in the HEK293 human embryonic kidney cells. In contrast, Zn(2+) in 5, 10 or 20 microM concentrations did not induce expression of HO-1 in ARPE-19 cells or any other cells tested. These data suggest the superiority of Mn(2+) over Zn(2+) in preventing Cd(2+) uptake and accumulation in RPE to toxic levels. Further, induction of HO-1 by Mn(2+) could provide RPE with some resistance to enhanced oxidative stress arising from Cd(2+) accumulation in RPE as HO-1 is one of the frontline cellular antioxidant defense mechanisms.

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.

Treatment with salicylic acid decreases the effect of cadmium on photosynthesis in maize plants.

The present study investigated the possible mediatory role of salicylic acid (SA) in protecting photosynthesis from cadmium (Cd) toxicity. Seeds of maize (Zea mays L., hybrid Norma) were sterilized and divided into two groups. Half of the seeds were presoaked in 500 microM SA solution for only 6h, after which both groups were allowed to germinate for 3d and were then grown for 14d in Hoagland solution at 22/18 degrees C in a 16/8-h light/dark period and 120 micromolm(-2)s(-1) PAR. All seedlings (without H(2)O and SA controls) were transferred to Cd-containing solutions (10, 15, and 25 microM) and grown for 14d. The rate of CO(2) fixation and the activity of ribulose 1,5-bisphosphate carboxylase (RuBPC, EC 4.1.1.39) and phosphoenolpyruvate carboxylase (PEPC, EC 4.1.1.31) were measured. Changes in the levels of several important parameters associated with oxidative stress, namely H(2)O(2) and proline production, lipid peroxidation, electrolyte leakage, and the activities of antioxidative enzymes (superoxide dismutase (SOD, EC 1.15.1.1), ascorbate peroxidase (APX, EC 1.11.1.11), catalase (CAT, EC 1.11.1.6), and guaiacol peroxidase (POD, EC 1.11.1.7)) were measured. Exposure of the plants to Cd caused a gradual decrease in the shoot and root dry weight accumulation, with the effect being most pronounced at 25 microM Cd. Seed pretreatment with SA alleviated the negative effect of Cd on plant growth parameters. The same tendency was observed for the chlorophyll level. The rate of CO(2) fixation was lower in Cd-treated plants, and the inhibition was partially overcome in SA-pretreated plants. A drop in the activities of RuBPC and PEPC was observed for Cd-treated plants. Pretreatment with SA alleviated the inhibitory effect of Cd on enzyme activity. Proline production and the rates of lipid peroxidation and electrolyte leakage increased in Cd-treated plants, whereas the values of these parameters were much lower in SA-pretreated plants. Treatment of plants with Cd decreased APX activity, but more than doubled SOD activity. Pretreatment with SA caused an increase in both APX and SOD activity, but caused a strong reduction in CAT activity. The data suggest that SA may protect cells against oxidative damage and photosynthesis against Cd toxicity.

Methylene blue delays cellular senescence and enhances key mitochondrial biochemical pathways.

Methylene blue (MB) has been used clinically for about a century to treat numerous ailments. We show that MB and other diaminophenothiazines extend the life span of human IMR90 fibroblasts in tissue culture by >20 population doubling (PDLs). MB delays senescence at nM levels in IMR90 by enhancing mitochondrial function. MB increases mitochondrial complex IV by 30%, enhances cellular oxygen consumption by 37-70%, increases heme synthesis, and reverses premature senescence caused by H2O2 or cadmium. MB also induces phase-2 antioxidant enzymes in hepG2 cells. Flavin-dependent enzymes are known to use NAD(P)H to reduce MB to leucomethylene blue (MBH2), whereas cytochrome c reoxidizes MBH2 to MB. Experiments on lysates from rat liver mitochondria suggest the ratio MB/cytochrome c is important for the protective actions of MB. We propose that the cellular senescence delay caused by MB is due to cycling between MB and MBH2 in mitochondria, which may partly explain the increase in specific mitochondrial activities. Cycling of MB between oxidized and reduced forms may block oxidant production by mitochondria. Mitochondrial dysfunction and oxidative stress are thought to be key aberrations that lead to cellular senescence and aging. MB may be useful to delay mitochondrial dysfunction with aging and the decrease in complex IV in Alzheimer disease.

28-homobrassinolide protects chickpea (Cicer arietinum) from cadmium toxicity by stimulating antioxidants.

In the present experiment the seeds of Cicer arietinum (L.) cv. Uday were inoculated with specific Rhizobium grown in sandy loam soil and were allowed to grow for 15 days. At this stage, the seedlings were supplied with 0, 50, 100 or 150 microM of cadmium in the form of cadmium chloride and sprayed with 0.01 microM of 28-homobrassinolide (HBL) at 30-day stage. The data indicated that plant fresh and dry mass, number of nodules, their fresh and dry mass, leghemoglobin content, nitrogen and carbohydrate content in the nodules, leaf chlorophyll content, nitrate reductase and carbonic anhydrase activities decreased proportionately with the increasing concentrations of cadmium but the content of proline and the activities of catalase, peroxidase and superoxide dismutase increased. The ill effect, generated by cadmium, was overcome if the stressed plants were sprayed with HBL.

The role of thiol-reducing agents on modulation of glutamate binding induced by heavy metals in platelets.

In the present study, we investigated if thiol-reducing agents are capable of altering mercury (Hg2+), lead (Pb2+) and cadmium (Cd2+) effects on platelet glutamatergic system. Dimercaprol (BAL), a dithiol chelating agent therapeutically used for the treatment of heavy metals poisoning, was capable of protecting the [3H]-glutamate binding against the effects caused by Pb2+ and Hg2+. 2,3-Dimercaptopropane-1-sulfonic acid (DMPS), another dithiol-reducing chelating agent, was capable of protecting the effect caused by Cd2+, Pb2+ and Hg2+. The similar effect was observed with addition of dithiothreitol (DTT) on [3H]-glutamate binding in human platelets. Dithiol-reducing agents (BAL, DMPS and DTT) alone did not alter [3H]-glutamate binding. In contrast, reduced glutathione (GSH), a monothiol-reducing agent, caused a significant inhibition on [3H]-glutamate binding at all concentrations tested. GSH did not modify heavy metal effects on [3H]-glutamate binding in platelets. The findings of the present investigation indicate that dithiol-reducing agents are capable of altering Hg2+, Pb2+ and Cd2+ effects on platelet glutamatergic system. In vitro data on chelating-metal interactions provide only an estimated guide to the treatment of heavy metal poisoning. Consequently, more studies in intoxicated patients are necessary to determine the precise use of the peripheral models and chelating agents.

The protective effect of selenium inorganic forms against cadmium and silver toxicity in mycelia of Pleurotus ostreatus.

The effect of two inorganic selenium forms has been investigated in the mycelia of Pleurotus ostreatus exposed to cadmium and silver salts in the shaken cultures. The degree of toxicity was assessed by the determination of malondialdehyde (MDA; a common biomarker of lipid peroxidation). The mycelia were exposed to one element form (up to 5 mg l(-1)) and also to the following combinations: cadmium(II) + selenium(IV); cadmium(II) + selenium(VI); silver(I) + selenium(IV); silver(I) + selenium(VI). The concentrations of cadmium, silver, selenium, and MDA were assessed in the mixed cytosol and cell membrane fractions (CCM). A positive correlation between MDA and cadmium was found in the CCM (beta=0.7775, P=0.0001), whereas the effect of silver was less significant (beta=0.4642, P=0.039). These results indicate that silver(I) and cadmium(II) have different capacities to induce lipid peroxidation in P. ostreatus. The protective role of selenium against metal-induced oxidative damage was found to be dependent on the oxidation state of the element form in the growth medium. The strongest beneficial effect was observed in mycelia exposed to cadmium(II) + selenium(IV) (inverse correlation between MDA and selenium in the CCM: beta=-0.7129, P=0.009) and it has been ascribed to a lower incorporation of the toxic metal and/or to possible intracellular interaction between selenium and cadmium. Under exposure to silver(I), the protective effect of selenium(IV) was less noticeable (correlation between MDA and selenium in the CCM; beta=-0.6068, P=0.036); in the presence of selenium(VI), no beneficial effect was observed.

Melatonin prevents the estrogenic effects of sub-chronic administration of cadmium on mice mammary glands and uterus.

Cadmium (Cd) is a heavy metal classified as a human carcinogen. Occupational exposure, dietary consumption and cigarette smoking are sources of Cd contamination. Cd-induced carcinogenicity depends on its oxidative and estrogenic actions. A possible role of Cd in breast cancer etiology has been recently suggested. Melatonin, because of its antioxidant and antiestrogenic properties could counteract the toxic effects of this metalloestrogen. Our aim was both to determine the effects of relevant doses of Cd on mice mammary glands and uterus and to test whether melatonin would counteract its effects. Female mice of different ages and estrogenic status (prepuberal, adult intact, adult ovariectomized) were treated with CdCl(2) (2-3 mg/kg, i.p.), melatonin (10 microg/mL in drinking water), CdCl(2) + melatonin, or diluents. Whereas in prepuberal animals Cd disturbs mammary ductal growth and reduces the number of terminal end buds, in adults, regardless of the steroidal milieu, Cd exerts estrogenic effects on mammary glands, increasing lobuloalveolar development and ductal branching. Uterine weight also increased as a result of Cd treatment. The effects of Cd are partially inhibited by melatonin. In adult ovariectomized mice, Cd concentration in blood of animals treated with CdCl(2) + melatonin was lower than in mice receiving only Cd; the opposite effects were found in non-castrated animals. As Cd mimics the effect of estrogens, the high incidence of breast cancer in tobacco smokers and women working in industries related with Cd could be explained because of the properties of this metal. The effects of melatonin point to a possible role of this indoleamine as a preventive agent for environmental or occupational Cd contamination.

Cytoprotective effects of selenium on cadmium-induced LLC-PK1 cells apoptosis by activating JNK pathway.

Extensive studies have indicated that the apoptosis pathway appears to be associated with intracellular reactive oxygen species (ROS) production in cadmium-induced nephrotoxicity, however, the precise cellular mechanism remains unclear. The purpose of this study was to determine the relationships between the activation of phosphorylated c-jun N-terminal kinase (JNK) and cadmium-induced apoptosis, and assess the possible cytoprotective mechanism of selenium. Our study clearly revealed cadmium treatment caused apoptosis in LLC-PK1 cells, which was partially suppressed by pretreatment with selenium, an antioxidant nutrient. Further studies found the phosphorylation of JNK kinase increased with exposure to cadmium for 3 h, even remained elevated at 9 h in the time course study, and the activation of phosphorylated JNK was detected in a dose-dependent manner. In addition, a concomitant time-dependent increase in caspase-3 activities was observed by cadmium treatment. During the process, selenium played the same role as N-acetyl-L-cysteine (NAC), a free radical scavenger. Pretreatment of cells with selenium partially suppressed of the phosphorylation of JNK, coupled with caspase-3 activation involved in cadmium-induced apoptosis. In conclusion, our studies provided a molecular linkage between the phosphorylation of JNK and cadmium-induced LLC-PK1 cells apoptosis, and demonstrated selenium also contributed a potentially protection to prevent cadmium-cytotoxicity.

Cadmium induces Ca2+-dependent necrotic cell death through calpain-triggered mitochondrial depolarization and reactive oxygen species-mediated inhibition of nuclear factor-kappaB activity.

This study investigates the mechanism of cell death induced by cadmium (Cd) in Chinese hamster ovary (CHO) cells. Cells exposed to 4 microM Cd for 24 h did not show signs of apoptosis, such as DNA fragmentation and caspase-3 activation. The pro-apoptotic (Bax) or anti-apoptotic (Bcl-2 and Bcl-xL) protein levels in the Bcl-2 family were not altered. However, an increase in propidium iodide uptake and depletion of ATP, characteristics of necrotic cell death, were observed. Cd treatment increased the intracellular calcium (Ca2+) level. Removal of the Ca2+ by a chelator, BAPTA-AM, efficiently inhibited Cd-induced necrosis. The increased Ca2+ subsequently mediated calpain activation and intracellular ROS production. Calpains then triggered mitochondrial depolarization resulting in cell necrosis. Cyclosporin A, an inhibitor of mitochondrial permeability transition, recovered the membrane potential and reduced the necrotic effect. The generated ROS reduced basal NF-kappaB activity and led cells to necrosis. An increase of NF-kappaB activity by its activator, PMA, attenuated Cd-induced necrosis. Calpains and ROS act cooperatively in this process. The calpain inhibitor and the ROS scavenger synergistically inhibited Cd-induced necrosis. Results in this study suggest that Cd stimulates Ca2+-dependent necrosis in CHO cells through two separate pathways. It reduces mitochondrial membrane potential by activating calpain and inhibits NF-kappaB activity by increasing the ROS level.