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 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 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. I. Messaoudi and J. El Heni have equally contributed to this work.     

Involvement of the synapse-specific zinc transporter ZnT3 in cadmium-induced hippocampal neurotoxicity

The present study examined the involvement of zinc (Zn)-transporters (ZnT3) in cadmium (Cd)-induced alterations of Zn homeostasis in rat hippocampal neurons. We treated primary rat hippocampal neurons for 24 or 48 hr with various concentrations of CdCl₂ (0, 0.5, 5, 10, 25, or 50 μM) and/or ZnCl ₂ (0, 10, 30, 50, 70, or 90 μM), using normal neuronal medium as control. By The CellTiter 96 ^® Aqueous One Solution Cell Proliferation Assay (MTS; Promega, Madison, WI) assay and immunohistochemistry for cell death markers, 10 and 25 μM of Cd were found to be noncytotoxic doses, and both 30 and 90 μM of Zn as the best concentrations for cell proliferation. We tested these selected doses. Cd, at concentrations of 10 or 25 μM (and depending on the absence or presence of Zn), decreased the percentage of surviving cells. Cd-induced neuronal death was either apoptotic or necrotic depending on dose, as indicated by 7-AAD and/or annexin V labeling. At the molecular level, Cd exposure induced a decrease in hippocampal brain-derived neurotrophic factor-tropomyosin receptor kinase B (BDNF-TrkB) and Erk1/2 signaling, a significant downregulation of the expression of learning- and memory-related receptors and synaptic proteins such as the NMDAR NR2A subunit and PSD-95, as well as the expression of the synapse-specific vesicular Zn transporter ZnT3 in cultured hippocampal neurons. Zn supplementation, especially at the 30 μM concentration, led to partial or total protection against Cd neurotoxicity both with respect to the number of apoptotic cells and the expression of several genes. Interestingly, after knockdown of ZnT3 by small interfering RNA transfection, we did not find the restoration of the expression of this gene following Zn supplementation at 30 μM concentration. These data indicate the involvement of ZnT3 in the mechanism of Cd-induced hippocampal neurotoxicity.     

Characterization of cadmium concentration and translocation among ramie cultivars as affected by zinc and iron deficiency

Zn and Fe are essential nutritional elements in plants and play important roles in various physiological processes of plants. Zn and Fe are chemically similar to cadmium (Cd); therefore, Zn and Fe may mediate Cd-induced physiological or metabolic changes in plants. In order to evaluate the interaction between Cd, Zn and Fe, we conducted a hydroponics experiment to determine the plant biomass, photosynthetic characteristics, and Cd accumulation of ten ramie cultivars under Zn/Fe-sufficient or Zn/Fe-deficient conditions in the presence of 32 µM CdCl₂. Ramie varied among cultivars in morpho-physiological response to Cd stress as well as Cd accumulation, translocation and distribution. Zn and Fe deficiency increased the concentration and amount of Cd in plant organs, but decreased TF_{stem to leaf} and TF_{root to stem}. Cultivars with more Cd in roots and shoots showed smaller increase in Cd accumulation under Zn and Fe-deficiency stress. Xiangzhu 7 and Duobeiti 1 showed a higher capacity of Cd accumulation in their shoots. Zn and Fe deficiency decreased Pn, but increased Ci, Gs, and E in most cultivars. The difference in Cd translocation among ramie cultivars was mainly ascribed to the difference in plant transpiration.     

Root morphology, root-hair development and rhizosheath formation on perennial grass seedlings is influenced by soil acidity

Cadmium (Cd) exerts a detrimental effect on the metabolism of plants, whereas selenium (Se) may protect them against various stressors through its antioxidative activity. In this in vitro study we investigated the impact of Se (2 µM Na₂SeO₄) on the growth, nutrient (P, S, K, Ca, Mg, B, Mn, Fe and Zn) concentrations and cell integrity of rape (Brassica napus oleifera) and two wheat (Triticum aestivum) genotypes subjected to Cd stress (600 µM CdCl₂). Rape accumulated both Cd and Se more than did wheat. In all plants, Cd markedly reduced the biomass, enhanced lipid peroxidation and diminished plasmalemma fluidity. A drop in the K uptake and the reduced plasmalemma permeability diminished the K efflux from the leaf cells. In contrast, Cd elevated S concomitantly with Zn, indicating an activity of detoxifying SH groups and SOD isoenzymes. When added alone, Se promoted the growth of all plants, it enhanced the accumulation of S, but the impact on other nutrients remained minor. In Cd-stressed plants, Se tended to counterbalance the Cd-induced changes in nutrients, it also reduced the lipid peroxidation and exerted positive effects on the cell membrane stability. The Cd stress and the protective role of Se were most evident in rape. The Finnish wheat genotype was less tolerant to Cd than the Polish one.     

Induction of necrosis in cadmium-induced hepatic oxidative stress and its prevention by the prophylactic properties of taurine

The present study has been carried out to investigate the protective role of taurine against cadmium (Cd)-induced oxidative impairment in murine liver. Oral administration of cadmium chloride (CdCl₂) at a dose of 4 mg/kg body weight for 6 days increased the accumulation of the Cd in the liver and diminished the liver weight to body weight ratio. The CdCl₂ altered the levels of intracellular trace elements, cofactors of various metalloenzymes and increased the activities of serum marker enzymes related to liver dysfunction. In addition, Cd intoxication also attenuated intracellular antioxidant power, the activities of antioxidant enzymes as well as the levels of cellular metabolites. Moreover, level of hepatic metallothionein, lipid peroxidation, protein carbonylation, DNA fragmentation, concentration of intracellular reactive oxygen species (ROS) and the activities of cytochrome P450s have been increased due to Cd toxicity. In addition to the oxidative impairments, Cd exposure caused hepatic cell death mainly via the necrotic pathway. Oral administration of taurine at a dose of 100 mg/kg body weight for 5 days prior to CdCl₂ intoxication prevented the alterations of all the toxic-induced hepatic damages. Histological studies also supported the beneficial role of taurine against Cd-induced hepatic damages. Combining all, results suggest that taurine could protect hepatic tissues against Cd-induced oxidative stress probably through its antioxidant activity.     

Testicular Histomorphometry and Ultrastructure of Rats Treated with Cadmium and Ginkgo biloba

The aim of this study is to investigate the association of a single low dose of Cd and daily doses of Ginkgo biloba extract (GbE) on the testis and accessory glands of rats. The animals were treated with a single dose of 3 µmol/kg body weight of cadmium chloride (CdCl₂) and/or 100 mg/kg body weight of GbE. The plasma testosterone levels; corporal, testicular, and accessory glands weight; gonadosomatic index, volumetric proportion; and absolute volume of testicular components did not change after the treatments. CdCl₂ caused significant reduction in Leydig cells volume and altered Leydig cell morphology, as well as vacuolated Sertoli cells cytoplasm, irregular chromatin condensation of late spermatids, and modified acrosome formation. However, animals that received GbE did not show these alterations. The reversal of Cd-induced alterations by the extract is a strong indication that G. biloba is helpful in diminishing the effect of Cd toxicity.     

Exogenous Selenium Pretreatment Protects Rapeseed Seedlings from Cadmium-Induced Oxidative Stress by Upregulating Antioxidant Defense and Methylglyoxal Detoxification Systems

The protective effect of selenium (Se) on antioxidant defense and methylglyoxal (MG) detoxification systems was investigated in leaves of rapeseed (Brassica napus cv. BINA sharisha 3) seedlings under cadmium (Cd)-induced oxidative stress. Two sets of 11-day-old seedlings were pretreated with both 50 and 100???M Se (Na₂SeO₄, sodium selenate) for 24?h. Two concentrations of CdCl₂ (0.5 and 1.0?mM) were imposed separately or on the Se-pretreated seedlings, which were grown for another 48?h. Cadmium stress at any levels resulted in the substantial increase in malondialdehyde and H₂O₂ levels. The ascorbate (AsA) content of the seedlings decreased significantly upon exposure to Cd stress. The amount of reduced glutathione (GSH) increased only at 0.5?mM CdCl₂, while glutathione disulfide (GSSG) increased at any level of Cd, with concomitant decrease in GSH/GSSG ratio. The activities of ascorbate peroxidase (APX) and glutathione S-transferase (GST) increased significantly with increased concentration of Cd (both at 0.5 and 1.0?mM CdCl₂), while the activities of glutathione reductase (GR) and glutathione peroxidase (GPX) increased only at moderate stress (0.5?mM CdCl₂) and then decreased at 1.0?mM severe stress (1.0?mM CdCl₂). Monodehydroascorbate reductase (MDHAR), dehydroascorbate reductase (DHAR), catalase (CAT), glyoxalase I (Gly I), and glyoxalase II (Gly II) activities decreased upon exposure to any levels of Cd. Selenium pretreatment had little effect on the nonenzymatic and enzymatic components of seedlings grown under normal conditions; i.e., they slightly increased the GSH content and the activities of APX, GR, GST, and GPX. On the other hand, Se pretreatment of seedlings under Cd-induced stress showed a synergistic effect; it increased the AsA and GSH contents, the GSH/GSSG ratio, and the activities of APX, MDHAR, DHAR, GR, GPX, CAT, Gly I, and Gly II which ultimately reduced the MDA and H₂O₂ levels. However, in most cases, pretreatment with 50???M Se showed better results compared to pretreatment with 100???M Se. The results indicate that the exogenous application of Se at low concentrations increases the tolerance of plants to Cd-induced oxidative damage by enhancing their antioxidant defense and MG detoxification systems.     

Cadmium-induced synthesis of HSP70 and a role of glutathione in Euglena gracilis

Abstract

The effect of cadmium-induced oxidative stress, with or without glutathione supplementation, was investigated in the single cell eukaryotic phytoflagellate, Euglena gracilis strains Z and its achlorophyllous mutant SMZ as experimental models. Both these strains actively synthesize thiols to prevent or resist cadmium toxicity. The content of glutathione, as a representative antioxidant, was also examined in both strains. Exposure to cadmium induced heat-shock protein 70 (HSP70) synthesis in both strains of E. gracilis. Glutathione supplementation also induced HSP70. Overall, these results indicate that glutathione was closely linked to the induction of stress-related proteins. The sensitivity to cadmium-stress was higher in strain Z than SMZ. The results suggest that chloroplasts may have a role in the regulation of HSP70 expression. The relationship between HSP70 and GSH levels is still far from understood, and further research may shed light upon their up-regulation in the presence of Cd.     

The role of zinc chelate of hydroxy analogue of methionine in cadmium toxicity: effects on cadmium absorption on intestinal health in piglets

Cadmium (Cd) is a toxic heavy metal that poses a threat to the health of humans and animals. It can cause serious damage to the small intestine, which is the main absorption site of Cd and the primary target organ after oral administration. Our previous study found that zinc chelate of hydroxy analogue of methionine (Zn-HMTB), a new type of feed additive, decreased Cd accumulation in the liver and kidneys. The aim of this study was to investigate the effect of Zn-HMTB on Cd absorption and Cd-induced toxicity in the small intestine of piglets. Twenty-four piglets (Landrace × Large White, 13.22 ± 0.58 kg BW) were randomly divided into four dietary treatment groups: basal diet, and diets containing 30 mg/kg Cd from CdCl₂ and 0, 100 or 200 mg/kg Zn from Zn-HMTB. The experiment lasted 27 days. The feed intake and final BW of each piglet were recorded at the end of the experiment. Gastrointestinal (GI) tract tissue and samples of liver, kidney, spleen, heart, lung and longissimus muscle tissue and faeces were collected. The concentrations of Cd and metal trace elements in the GI tract and organs were analysed, as was the relative messenger RNA (mRNA) expression of inflammatory cytokines and metal element transporters in the small intestine, and epithelial apoptosis in the small intestine. The results showed that, compared with Cd-treated piglets, piglets in the Zn-HMTB and Cd cotreatment groups had less Cd deposition in the stomach, ileum, caecum, colon, liver, kidneys, spleen, lungs, heart and muscles (P < 0.05), and lower Cd concentrations in faeces (P < 0.05), suggesting that Zn-HMTB increased Cd absorption and the excretion of Cd in other forms (possibly urine). Zinc chelate of hydroxy analogue of methionine increased Zn deposition in the jejunum and the relative mRNA expression of divalent metal transporters 1 and zinc transporter 5 in the duodenum (P < 0.05), indicating that Zn-HMTB may promote the absorption and transportation of Cd and Zn together by upregulating metal element transporters. Competition between Zn and Cd may be responsible for accelerating Cd excretion. Furthermore, Zn-HMTB reduced Cd-induced apoptosis of enterocytes and inflammatory stimuli in the small intestine, suggesting that Zn-HMTB reduced Cd-induced toxicity to the small intestine. These results suggest that Zn-HMTB can be helpful in decreasing Cd accumulation in the GI tract and organs of piglets and relieving Cd-induced toxicity to the small intestine but cannot reduce the absorption of Cd.     

Effects of cadmium on gene expression in cadmium-tolerant and cadmium-sensitiveDatura innoxia cells

The effect of Cd on gene expression in suspension cultures of twoDatura innoxia cell lines with differing Cd tolerance was studied.In vivo labeling experiments using [³H] leucine showed that Cd induced the synthesis of a similar range of proteins in both cell lines at a concentration which will kill the sensitive but not the tolerant cells. Corresponding changes in levels of translatable mRNA were also observed. The induction of the synthesis of proteins by Cd was transient since Cd-tolerant cells growing continuously in 250 M CdCl₂ contained a similar set ofin vitro translation products to cells growing in the absence of Cd. Although Cd had a similar effect on gene expression in both cell lines, Cd-tolerant cells possess two abundant mRNAs which are constitutively produced. These mRNAs encode proteins of low molecular weight (about 11 kDa) and are either absent or present at a low level in Cd-sensitive cells. The functions of these proteins are not known but they may be involved in the tolerance mechanism. Two-dimensional gel electrophoresis ofin vitro translation products showed that many of the Cd-induced proteins are also induced by heat shock. A 42°C heat shock resulted in agreater range and more intense induction of translatable mRNAs than 4 h exposure to 250 M CdCl₂. However a subset of mRNAs were induced specifically by Cd while other mRNAs were heat shock-specific. There was no difference in the ability of the two cell lines to tolerate heat shock. This was also reflected by the same pattern of major proteins induced by heat shock in the two cell lines.     

Influence of zinc on cadmium-induced toxicity in nodules of pigeonpea (Cajanus cajan L. Millsp.) inoculated with arbuscular mycorrhizal (AM) fungi

Arbuscular mycorrhizal (AM) fungi are known to alleviate heavy-metal stress in plants. The intent of the present work was to analyze accumulation of heavy metals (Cd and Zn) in nodules of two Cajanus cajan (L.) Millsp. genotypes and their subsequent impact on nitrogen fixation, oxidative stress, and non-protein thiols (glutathione and phytochelatins) with and without AM fungus Glomus mosseae. Accumulation of Cd and Zn in nodules resulted in sharp reduction in nodule number, nodule dry mass as well as nitrogen fixation (leghemoglobin and nitrogenase (N₂ase)), although Cd had more pronounced effects than Zn. Cd-induced lipid peroxidation, H₂O₂ accumulation, and electrolyte leakage were largely reversed by Zn supplementation. Zn application significantly altered the negative effects of Cd on the synthesis of non-protein thiols, suggesting antagonistic behaviour of Zn. Higher concentration of Zn was more effective in lessening the negative effects of Cd than its lower concentration. Remarkable genotypic variation was found, with more severe effects of both the metals in P792 than Sel 85N. Glomus mosseae attenuated the phytotoxic effects of metals in nodules by decreasing metal uptake, oxidative stress, and by enhancing defense system ultimately leading to better nitrogen-fixing potential of pigeonpea nodules.     

Cadmium induced Drp1-dependent mitochondrial fragmentation by disturbing calcium homeostasis in its hepatotoxicity

Mitochondria are critical targets in the hepatotoxicity of cadmium (Cd). Abnormal mitochondrial dynamics have been increasingly implicated in mitochondrial dysfunction in pathophysiological conditions. Therefore, our study aimed to investigate the effects and underlying mechanism of Cd on mitochondrial dynamics during hepatotoxicity. In the L02 liver cell lines, 12 μM cadmium chloride (CdCl₂) exposure induced excessive mitochondrial fragmentation as early as 3 h post-treatment with Cd, which preceded the mitochondrial dysfunction such as reactive oxygen species (ROS) overproduction, mitochondrial membrane potential (ΔΨm) loss and ATP reduction. Concurrent to mitochondrial fragmentation, CdCl₂ treatment increased the protein levels of dynamin-related protein (Drp1) and promoted the recruitment of Drp1 into mitochondria. Strikingly, mitochondrial fragmentation also occurred in the liver tissue of rats exposed to CdCl₂, accompanied by enhanced recruitment of Drp1 into mitochondria. Moreover, in L02 cells, Drp1 silencing could effectively reverse Cd-induced mitochondrial fragmentation and mitochondrial dysfunction. Furthermore, the increased expression and mitochondrial recruitment of Drp1 were tightly related to the disturbance of calcium homeostasis, which could be prevented by both chelating [Ca²⁺]_i and inhibiting [Ca²⁺]_m uptake. Overall, our study indicated that Cd induced Drp1-dependent mitochondrial fragmentation by disturbing calcium homeostasis to promote hepatotoxicity. Manipulation of Drp1 may be the potential avenue for developing novel strategies to protect against cadmium-induced hepatotoxicity.     

Cadmium induces vascular permeability via activation of the p38 MAPK pathway

The vasculature of various organs is a targeted by the environmental toxin, cadmium (Cd). However, mechanisms leading to pathological conditions are poorly understood. In the present study, we examined the effect of cadmium chloride (CdCl₂) on human umbilical vein endothelial cells (HUVECs). At 4 μM, CdCl₂ induced a hyper-permeability defect in HUVECs, but not the inhibition of cell growth up to 24 h. This effect of CdCl₂ was dependent on the activation of the p38 mitogen-activated protein kinase (MAPK) pathway. The p38 MAPK inhibitor SB203850 suppressed the CdCl₂-induced alteration in trans-endothelial electrical resistance in HUVEC monolayers, a model measurement of vascular endothelial barrier integrity. SB203850 also inhibited the Cd-induced membrane dissociation of vascular endothelial (VE) cadherin and β-catenin, the important components of the adherens junctional complex. In addition, SB203850 reduces the Cd-induced expression and secretion of tumor necrosis factor α (TNF-α). Taken together, our findings suggest that Cd induces vascular hyper-permeability and disruption of endothelial barrier integrity through stimulation of p38 MAPK signaling.     

The Effect of Selenium on the Cd-Induced Apoptosis via NO-Mediated Mitochondrial Apoptosis Pathway in Chicken Liver

Cd-induced apoptosis and the protective effects of Se against Cd-induced injury have been reported in previous studies. However, little is known regarding the effects of Cd-induced apoptosis in hepatic cells and the antagonistic effects of Se on Cd in poultry. In the present study, 128 healthy 31-week-old laying hens were randomly divided into four groups, which were fed basic diets, with the addition of Se (Na₂SeO₃, 2 mg/kg), Cd (CdCl₂, 150 mg/kg), or Se + Cd (150 mg/kg of CdCl₂ and 2 mg/kg of Na₂SeO₃) for 90 days. Ultrastructural changes, nitric oxide (NO) concentrations, inducible nitric oxide synthase (iNOS) activities, results of the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay of apoptosis, and the expression of iNOS and apoptosis-related genes in livers were determined. It was observed that Cd treatment significantly increased the concentrations of NO and iNOS activity in chicken livers. The production of excessive NO initiated the mitochondrial apoptotic pathway. Exposure to Cd increased the mRNA and the protein expression levels of iNOS, caspase-3, Bax, p53, and Cyt-c. Furthermore, the ratio of Bax/Bcl-2 increased, while the expression of Bcl-2 decreased. Treatment with Se significantly alleviated Cd-induced apoptosis in chicken livers, as evidenced by a reduction in the production of NO, iNOS activity, the number of apoptotic cells, and mRNA and protein expression levels of iNOS, caspase-3, Bax, and Cyt-c. It indicated that Cd induced NO-mediated apoptosis through the mitochondrial apoptotic pathway and Se exerted antagonizing effects. The present study provides new insights as to how Se affects Cd-induced toxicity in the chicken liver.     

The role of endoplasmic reticulum in cadmium-induced mesangial cell apoptosis

Cd is an industrial and environmental pollutant that affects many organs in humans and other mammals. However, the molecular mechanisms of Cd-induced nephrotoxicity are unclear. In this study, we show that endoplasmic reticula (ER) played a pivotal role in Cd-induced apoptosis in mesangial cells. Using Fluo-3 AM, the intracellular concentration of calcium ([Ca²⁺]_i) was detected as being elevated as time elapsed after Cd treatment. Co-treatment with BAPTA-AM, a calcium chelator, was able to significantly suppress Cd-induced apoptosis. Calcineurin is a cytosolic phosphatase, which was able to dephosphorylate the inositol-1,4,5-triphosphate receptor (IP₃R) calcium channel to prevent the release of calcium from ER. Cyclosporine A, a calcineurin inhibitor, increased both [Ca²⁺]_i and the percentage of Cd-induced apoptosis. However, EGTA and the IP₃R inhibitor, 2-APB, were able to partially modulate Cd cytotoxicity. These results led us to suggest that the extracellular and ER-released calcium plays a crucial role in Cd-induced apoptosis in mesangial cells. Following this line, we further detected the ER stress after Cd treatment since ER is one of the major calcium storage organelles. After Cd exposure, GADD153, a hallmark of ER stress, was upregulated (at 4 h of exposure), followed by activation of ER-specific caspase-12 and its downstream molecule caspase-3 (at 16 h of exposure). The pan caspase inhibitor, Z-VAD, and BAPTA-AM were able to reverse the Cd-induced cell death and ER stress, respectively. Furthermore, the mitochondrial membrane potential (ΔΨ_m) was depolarized significantly and cytochrome c was released after 24 h of exposure to Cd and followed by mild activation of caspase-9 at the 36-h time point, indicating that mitochondria stress is a late event. Therefore, we concluded that ER is the major killer organelle in Cd-induced mesangial cell apoptosis and that calcium oscillation plays a pivotal role.     

Selenium Source Impacts Protection of Porcine Jejunal Epithelial Cells from Cadmium-Induced DNA Damage,with Maximum Protection Exhibited with Yeast-Derived Selenium Compounds

Selenium (Se) is found in inorganic and organic forms, both of which are commonly used in animal feed supplements. The aim of this study was to determine the impact of the chemical form of Se on its associated ameliorative effects on cadmium (Cd)-induced DNA damage in a porcine model. At a cellular level, Cd mediates free oxygen radical production leading in particular to DNA damage, with consequential mutagenesis and inhibition of DNA replication. In this study, porcine jejunal epithelial cells (IPEC-J2) were pre-incubated for 48 h with one of Se-yeast (Sel-Plex), selenomethionine (Se-M), sodium selenite (Se-Ni) or sodium selenate (Se-Na). The effects of this supplementation on cell viability and DNA damage following cadmium chloride (CdCl₂) exposure were subsequently evaluated. IPEC-J2 cells were cultivated throughout in medium supplemented with porcine serum to generate a superior model that recapitulated the porcine gut epithelium. The results illustrated that Se antioxidant effects were both composition- and dose-dependent as evident from cell viability (Alamar Blue and 5-carboxyfluorescein diacetate acetoxymethyl ester) and DNA damage assays (Comet and TUNEL). Both the Se-yeast and Se-M organic species, when used at the European Food Safety Authority guideline levels, had a protective effect against Cd-induced DNA damage in the IPEC-J2 model system whereas for inorganic Se-Ni and Se-Na sources no protective effects were observed and in fact these were shown to enhance the negative effects of Cd-induced DNA damage. It can be concluded that nutritional supplementation with organoselenium may protect porcine gut integrity from damage induced by Cd.     

Protective effect of ascorbic acid on cadmium-induced hypertension and vascular dysfunction in mice

Cadmium (Cd) is one of the most important environmental pollutants that cause a number of adverse health effects in humans and animals. Recent studies have shown that Cd-induced oxidative damage within the vascular tissues results in vascular dysfunction. The current study was aimed to investigate whether ascorbic acid could protect against Cd-induced vascular dysfunction in mice. Male ICR mice were received CdCl₂ (100 mg/l) via drinking water for 8 weeks alone or received ascorbic acid supplementation at doses of 50 and 100 mg/kg/day for every other day. Results showed that Cd administration increased arterial blood pressure and blunted the vascular responses to vasoactive agents. These alterations were related to increased superoxide production in thoracic aorta, increased urinary nitrate/nitrite, increased plasma protein carbonyl, elevated malondialdehyde (MDA) concentrations in plasma and tissues, decreased blood glutathione (GSH), and increased Cd contents in blood and tissues. Ascorbic acid dose-dependently normalized the blood pressure, improved vascular reactivities to acetylcholine (ACh), phenylephrine (Phe) and sodium nitroprusside (SNP). These improvements were associated with significant suppression of oxidant formation, prevention of GSH depletion, and partial reduction of Cd contents in blood and tissues. The findings in this study provide the first evidence in pharmacological effects of ascorbic acid on alleviation of oxidative damage and improvement of vascular function in a mouse model of Cd-induced hypertension and vascular dysfunction. Moreover, our study suggests that dietary supplementation of ascorbic acid may provide beneficial effects by reversing the oxidative stress and vascular dysfunction in Cd-induced toxicity.     

Protective Effects of Selenium on Cadmium-Induced Brain Damage in Chickens

Selenium (Se) is an important dietary micronutrient with antioxidative roles. Cadmium (Cd), a ubiquitous environmental pollutant, is known to cause brain lesion in rats and humans. However, little is reported about the deleterious effects of subchronic Cd exposure on the brain of poultry and the protective roles on the brain by Se against Cd. The aim of this study was to investigate the protective effects of Se on Cd-induced brain damage in chickens. One hundred twenty 100-day-old chickens were randomly assigned to four groups and were fed a basal diet, or Se (as 10 mg Na₂SeO₃/kg dry weight of feed), Cd (as 150 mg CdCl₂/kg dry weight of feed), or Cd?+?Se in their basic diets for 60 days. Then, concentrations of Cd and Se, production of nitric oxide (NO), messenger RNA (mRNA) level and activity of inducible NO synthase (iNOS), level of oxidative stress, and histological and ultrastructural changes of the cerebrum and cerebellum were examined. The results showed that Cd exposure significantly increased Cd accumulation, NO production, iNOS activities, iNOS mRNA level, and MDA content in the cerebrum and cerebellum. Cd treatment obviously decreased Se content and antioxidase activities and caused histopathological changes in the cerebrum and cerebellum. Se supplementation during dietary Cd obviously reduced Cd accumulation, NO production, mRNA level and activity of iNOS, oxidative stress, and histopathological damage in the cerebrum and cerebellum of chickens. It indicated that Se ameliorates Cd-induced brain damage in chickens by regulating iNOS-NO system changes, and oxidative stress induced by Cd and Se can serve as a potential therapeutic for Cd-induced brain lesion of chickens.     

Accumulation of ammonium ion in cadmium tolerant and sensitive cultivars of Oryza sativa

Cd-tolerant and Cd-sensitive rice cultivars were used to study the role of NH₄ ⁺ accumulation in Cd-induced toxicity. NH₄ ⁺ accumulation seems to be involved in regulating the toxicity of rice seedlings caused by CdCl₂. This conclusion was based on the observations that (a) on treatment with CdCl₂, NH₄ ⁺ content increased rapidly in the leaves of the Cd-sensitive cultivar (cv. Taichung Native 1, TN1) but not in the Cd-tolerant cultivar (cv. Tainumg 67, TNG67), (b) pretreatment with abscisic acid (ABA) enhanced Cd tolerance and reduced Cd-induced NH₄ ⁺ accumulation in TN1 seedlings, (c) exogenous application of the ABA biosynthesis inhibitor, fluridone, decreased Cd tolerance and increased NH₄ ⁺ content in leaves of TNG67, (d) exogenous application of phosphinothricin, an inhibitor of glutamine synthetase (GS), which resulted in NH₄ ⁺ accumulation in the leaves, also induced toxicity similar to Cd in TN1 seedlings. Evidence is presented to show that Cd-induced NH₄ ⁺ accumulation in TN1 leaves is attributable to a decrease in GS activity. Since Cd-treated TN1 leaves had higher glutamine and glutamate contents than control leaves, it is unlikely that glutamine (or glutamate) depletion is the mechanism which regulates Cd-induced toxicity.