Cadmium-induced Oxidative Stress Research Articles

Effects of cadmium-induced oxidative stress on growth and nitrogen assimilation in blackgram [Vigna mungo (L.) Hepper

Cadmium (Cd) accumulation, oxidative damage, and nitrogen metabolism were studied in roots and leaves of 30-d-old blackgram plants [Vigna mungo (L.) Hepper], grown in a mixture of soil and compost (3:1) with different Cd concentrations. Significant reductions in both root and shoot dry weight were noted. The concentration of Cd in roots and leaves increased with increasing Cd levels. The level of lipid peroxidation elevated with a consequent increase in H2O2 content under Cd stress in both plant organs. The activity of enzymes mediating the nitrogen assimilation in roots and leaves was greatly reduced in the presence of Cd, except glutamate dehydrogenase (GDH) which showed a significant increase.

Protective effect of maifanite against cadmium-induced oxidative stress to rats hippocampus by regulating the balance and metabolism of metals

In this paper, the author reported the effect of maifanite on the learning and memory of rats suffering Cd poisoning by step-down and step-through test, analyzed the content of MDA, MT, SOD, and GSH-Px in the hippocampus of rats respectively, and assayed the content of Fe, Cu, Zn, Mn, Se, and Cd in the hippocampus of rats. In the step-down test, it is found that maifanite can reduce the number of electric shock, prolong step-down latency, and cut down error times when rats are exposed to Cd 24 h. In the step-through test, maifanite can obviously prolong the latency of entering the dark cabin of rats suffering Cd poisoning. The exogenous Cd can lead to the decrease of SOD and GSH-Px activity and the increase of MDA and MT content. The alternation of maifanite and Cd by the gavage can significantly increase the SOD and GSH-Px activity as well as MT content, while lessening the MDA content. The accumulation of exogenous Cd in hippocampus causes the increase of Zn, Fe, Mn, and Cd content, and the decrease of Cu and Se content. The intake of maifanite can regulate the imbalance of metals content and make its content near to the of level control group. The research shows that maifanite can improve the ability of learning and memory of rats suffering Cd poisoning, increase MT formation and lower hyperoxidative damage. Maifanite has the function of balancing the content of trace elements in rats suffering Cd poisoning, and meanwhile can alleviate the toxicity of Cd effectively.

Exogenous calcium alleviates the impact of cadmium-induced oxidative stress in Lens culinaris medic. Seedlings through modulation of antioxidant enzyme activities

The effect of calcium (Ca) on lentil (Lens culinaris Medic.) seedlings exposed to cadmium (Cd) stress was studied by investigating plant growth and antioxidant enzyme activities. Plants were grown for 14 days in full-strength Hoagland nutrient media supplemented with Cd concentrations of 0, 10, 20, and 40 μM, and on corresponding medium supplied with 5 mM Ca(NO3)2 prior to Cd addition. Increasing Cd led to accumulation of metal and reduced the fresh weight of the shoots more strongly than that of the roots. Cd concentrations of 20 and 40 μM were selected to study its toxic effect on seedlings. Activities of superoxide dismutase, ascorbate peroxidase, catalase, dehydroascorbate reductase, and glutathione reductase decreased at much higher magnitude in the shoots than those observed in the roots under Cd exposure. Failure of antioxidant defense in scavenging of reactive oxygen species was evidenced by abnormal rise in H2O2, resulting in enhancement of lipid peroxidation and membrane electrolyte leakage as the marks of Cd-induced oxidative stress in lentil seedlings. Ca priming in the media significantly reduced the Cd accumulation and considerably alleviated the adverse impact of Cd treatment by modulating the antioxidant enzyme activity. Mitigation of Cd-induced stress by Ca application was strongly suggested by declining levels of H2O2 and consequent lowering of oxidative damage of membrane. Consequently, this enhanced fresh mass of plant parts as the sign of Ca-mediated normal growth in Cd-treated lentil seedlings.

He–Ne laser pretreatment protects wheat seedlings against cadmium-induced oxidative stress

The aim of the investigation is to determine the effect of He–Ne laser pretreatment of wheat seeds on the resistance of seedlings to cadmium stress. Changes in physiological, biochemical and molecular characters were measured. Our results showed that 150μM Cd treatment significantly reduced plant height, root length, shoot fresh weight, shoot dry weight, root fresh weight, root dry weight, ascorbate acid (AsA) and glutathione (GSH) concentration, the activities of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), ascorbate peroxidase (APX) and gene expression levels of SOD, APX, enhanced the concentration of malondialdehyde (MDA), hydrogen peroxide (H2O2) and the rate of superoxide radical (O2•−) generation in the wheat seedlings when compared with the control. However, seeds with He–Ne laser pretreatment 5min conferred tolerance to cadmium stress in wheat seedlings by decreasing the concentration of MDA and H2O2, the rate of O2•− generation and increasing the gene expression levels of SOD, POD, APX, the activities of SOD, POD, CAT, APX and AsA and GSH concentration. These results suggest that those changes in MDA, O2•−, H2O2, anti-oxidative enzymes, gene expression level and anti-oxidative compounds are responsible for the increase in cadmium stress resistance observed in the experiments. The results also showed that the laser had a positive physiological effect on the growth of cadmium stressed seedlings. This is the first investigation reporting the use of He–Ne laser pretreatment to enhance of wheat seedlings tolerance to cadmium stress.

Role of Nrf2 antioxidant defense in mitigating cadmium-induced oxidative stress in the olfactory system of zebrafish

Exposure to trace metals can disrupt olfactory function in fish leading to a loss of behaviors critical to survival. Cadmium (Cd) is an olfactory toxicant that elicits cellular oxidative stress as a mechanism of toxicity while also inducing protective cellular antioxidant genes via activation of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway. However, the molecular mechanisms of Cd-induced olfactory injury have not been characterized. In the present study, we investigated the role of the Nrf2-mediated antioxidant defense pathway in protecting against Cd-induced olfactory injury in zebrafish. A dose-dependent induction of Nrf2-regulated antioxidant genes associated with cellular responses to oxidative stress was observed in the olfactory system of adult zebrafish following 24h Cd exposure. Zebrafish larvae exposed to Cd for 3h showed increased glutathione S-transferase pi (gst pi), glutamate–cysteine ligase catalytic subunit (gclc), heme oxygenase 1 (hmox1) and peroxiredoxin 1 (prdx1) mRNA levels indicative of Nrf2 activation, and which were blocked by morpholino-mediated Nrf2 knockdown. The inhibition of antioxidant gene induction in Cd-exposed Nrf2 morphants was associated with disruption of olfactory driven behaviors, increased cell death and loss of olfactory sensory neurons (OSNs). Nrf2 morphants also exhibited a downregulation of OSN-specific genes after Cd exposure. Pre-incubation of embryos with sulforaphane (SFN) partially protected against Cd-induced olfactory tissue damage. Collectively, our results indicate that oxidative stress is an important mechanism of Cd-mediated injury in the zebrafish olfactory system. Moreover, the Nrf2 pathway plays a protective role against cellular oxidative damage and is important in maintaining zebrafish olfactory function.

Effects of oral and intraperitoneal magnesium treatment against cadmium-induced oxidative stress in plasma of rats

Cadmium (Cd) has been recognised as one of the most important environmental and industrial pollutants, and up-to-date investigations have shown that one of the mechanisms of its toxicity is associated with the induction of oxidative stress. The aim of this study was to determine the connection between acute oral and intraperitoneal exposure to Cd and parameters indicative of oxidative stress in the plasma of rats, as well as to examine the potential protective effect of magnesium (Mg) in conditions of acute oral and intraperitoneal Cd poisoning. The experiment was performed on male albino Wistar rats (n=40) randomly divided into control group, Cdor group that received 30 mg kg-1 b.w. Cd by oral gavage, Cd+Mgor group that orally received 50 mg kg-1 b.w. Mg one hour before oral Cd, Cdip group that received 1.5 mg kg-1 b.w. Cd intraperitoneally, and Cd+Mgip group that intraperitoneally received 3 mg kg-1 b.w. Mg 10 min before intraperitoneal Cd. The animals were sacrificed 24 h after treatment and the following parameters were measured: superoxide dismutase activity, superoxide anion, total oxidative status, advanced oxidation protein products, and malondialdehyde. All parameters of oxidative stress in rat plasma were negatively affected by Cd treatment with more pronounced negative effects after intraperitoneal treatment, with the exception of superoxide dismutase (SOD) activity. Although both oral and intraperitoneal Mg pretreatment had protective effects, more pronounced beneficial effects were observed after oral administration, since it managed to completely prevent Cd-induced changes in the investigated parameters. The observed results support the use of Mg as potential protective agent against toxic effects caused by Cd.

Protective Effects of Glutathione and Lipoic Acid against Cadmium-Induced Oxidative Stress in Rat’s Kidney

Cadmium is a widespread, toxic industrial pollutant. The proximal tubule of the mammalian kidney is a major target of Cd-induced toxicity. We analyzed the effects of cadmium exposure on the model system of experimental animals, the thiobarbituric acid (TBA)-reactive substance (TBARS) level, and the activity of xanthine oxidase (XO) and catalase in kidney of rats, with and without glutathione and lipoic acid (LA). The experimental animals were classified into six groups, regarding cadmium, glutathione, and LA intake. The concentration of TBARSs in the homogenate was determined by spectrophotometric method according to Nabavi et al. The specific activity of XO was determined spectrophotometrically by the method of Aygul et al. Catalase activity in tissues was determined by spectrophotometric method according to Nabavi et al. The increased level of TBARS and the increased activity of XO in kidney tissue in cadmium poisoning are statistically significant compared to control (p < 0.001). Glutathione and LA applied along with cadmium lowered TBARS concentration and reduced XO activity (p < 0.001). Catalase activity in the kidney tissue was increased in the group, which was administered cadmium (p < 0.001). In conclusion, glutathione and LA, as physiological antioxidants applied with cadmium, have reduced the level of lipid peroxide and the activity of XO, and can be used as protectors in conditions of cadmium poisoning.

Cadmium-induced oxidative stress and histological damage in the myocardium. Effects of a soy-based diet

Cd exposure has been associated to an augmented risk for cardiovascular disease. We investigated the effects of 15 and 100ppm of Cd on redox status as well as histological changes in the rat heart and the putative protective effect of a soy-based diet. Male Wistar rats were separated into 6 groups and treated during 60days as follows: groups (1), (2) and (3) were fed a casein-based diet; groups (4), (5) and (6), a soy-based diet; (1) and (4) were given tap water; (2) and (5) tap water containing 15ppm of Cd2+; and (3) and (6) tap water containing 100ppm of Cd2+. Serum lipid peroxides increased and PON-1 activity decreased in group (3). Lipoperoxidation also increased in the heart of all intoxicated groups; however protein oxidation only augmented in (3) and reduced glutathione levels diminished in (2) and (3). Catalase activity increased in groups (3) and (6) while superoxide dismutase activity increased only in (6). Glutathione peroxidase activity decreased in groups (3) and (6). Nrf2 expression was higher in groups (3) and (6), and MTI expression augmented in (3). Histological examination of the heart tissue showed the development of hypertrophic and fusion of cardiomyocytes along with foci of myocardial fiber necrosis. The transmission electron microscopy analysis showed profound ultra-structural damages. No protection against tissue degeneration was observed in animals fed the soy-based diet. Our findings indicate that even though the intake of a soy-based diet is capable of ameliorating Cd induced oxidative stress, it failed in preventing cardiac damage.

Cadmium-induced oxidative stress and apoptosis in the testes of frog Rana limnocharis

This study explored the genetic damage induced by cadmium exposure in the testes of Rana limnocharis. Healthy adult frogs were exposed to 2.5, 5, 7.5, or 10mg/L of cadmium solution for 14 days. The results showed that exposure to these concentrations increased the levels of reactive oxygen species and malondialdehyde content in the testes, clearly indicating a dose–effect relationship. Moreover, the same dosages of Cd2+ solution increased glutathione (reduced) content, with the values being significantly different from those observed in the control group (P<0.01). The comet assay results demonstrated that the DNA damage rate, tail length, and tail moment of samples obtained from frogs exposed to 2.5–7.5mg/L of cadmium solution significantly increased compared with those of samples obtained from the control group (P<0.01). These findings suggest that cadmium can induce free radical generation, followed by lipid peroxidation and DNA damage. Ultrastructural observation revealed vacuoles in the spermatogenic cells, cell dispersion, incomplete cell structures, and deformed nucleoli. Moreover, cadmium exposure induced significant down-regulation of Bcl-2 expression and up-regulation of Bax and caspase-3 expressions. Taken together, these data indicate that cadmium can induce testicular cell apoptosis in R. limnocharis. Exploring the effects of cadmium on the mechanism of reproductive toxicity in amphibians will help provide a scientific basis accounting for the global population decline in amphibian species.

Nrf2 activation prevents cadmium-induced acute liver injury

Oxidative stress plays an important role in cadmium-induced liver injury. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that up-regulates cytoprotective genes in response to oxidative stress. To investigate the role of Nrf2 in cadmium-induced hepatotoxicity, Nrf2-null mice, wild-type mice, kelch-like ECH-associated protein 1-knockdown (Keap1-KD) mice with enhanced Nrf2, and Keap1-hepatocyte knockout (Keap1-HKO) mice with maximum Nrf2 activation were treated with cadmium chloride (3.5mg Cd/kg, i.p.). Blood and liver samples were collected 8h thereafter. Cadmium increased serum alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) activities, and caused extensive hepatic hemorrhage and necrosis in the Nrf2-null mice. In contrast, Nrf2-enhanced mice had lower serum ALT and LDH activities and less morphological alternations in the livers than wild-type mice. H2DCFDA (2′,7′-dichlorodihydrofluoresein diacetate) staining of primary hepatocytes isolated from the four genotypes of mice indicated that oxidative stress was higher in Nrf2-null cells, and lower in Nrf2-enhanced cells than in wild-type cells. To further investigate the mechanism of the protective effect of Nrf2, mRNA of metallothionein (MT) and other cytoprotective genes were determined. Cadmium markedly induced MT-1 and MT-2 in livers of all four genotypes of mice. In contrast, genes involved in glutathione synthesis and reducing reactive oxygen species, including glutamate-cysteine ligase (Gclc), glutathione peroxidase-2 (Gpx2), and sulfiredoxin-1 (Srxn-1) were only induced in Nrf2-enhanced mice, but not in Nrf2-null mice. In conclusion, the present study shows that Nrf2 activation prevents cadmium-induced oxidative stress and liver injury through induction of genes involved in antioxidant defense rather than genes that scavenge Cd.

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 μM Se (Na(2)SeO(4), sodium selenate) for 24 h. Two concentrations of CdCl(2) (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 H(2)O(2) 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 CdCl(2), 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 CdCl(2)), while the activities of glutathione reductase (GR) and glutathione peroxidase (GPX) increased only at moderate stress (0.5 mM CdCl(2)) and then decreased at 1.0 mM severe stress (1.0 mM CdCl(2)). 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 H(2)O(2) levels. However, in most cases, pretreatment with 50 μM Se showed better results compared to pretreatment with 100 μM 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.

Root adaptations to cadmium-induced oxidative stress contribute to Cd tolerance in the hyperaccumulator Sedum alfredii

Short-term responses of Sedum alfredii roots to Cd exposure was compared in Cd hyperaccumulator (HE) and nonhyperaccumulating ecotype (NHE). Cadmium exposure significantly inhibited root elongation and induced loss of plasma membrane integrity and lipid peroxidation of roots tips in the NHE, whereas these effects were much less pronounced in the HE plants. A strong accumulation of reactive oxygen species with increasing Cd concentration was noted in the NHE root tips, but not in HE. After Cd exposure, a dose-dependent decrease in oxidized glutathione and marked increase in reduced glutathione and non-protein thiols were observed in root tips of HE, but were not seen in the NHE plants. These results suggest that the HE tolerates high Cd in the environment through the differential adaptations against Cd-induced oxidative stress.

Protective effect of aqueous Curry leaf (Murraya koenigii) extract against cadmium-induced oxidative stress in rat heart

Treatment of rats with a low dose of cadmium chloride caused a significant damage in the rat cardiac tissue indicated by the increase in the level of serum glutamate oxaloacetate transaminase and lactate dehydrogenase1 activities. Histological studies confirmed the damage due to cadmium. That cadmium-induced tissue damage was caused due to oxidative stress was evident from the changes observed in the levels of lipid peroxidation and reduced glutathione, the protein carbonyl content, and the alterations in the activities of cardiac antioxidant and pro-oxidant enzymes. Treatment of rats with cadmium also caused alterations in the activities of mitochondrial Kreb’s cycle as well as respiratory chain enzymes. All these changes were ameliorated when the rats were pre-treated with an aqueous extract of Curry leaf (Murraya koenigii). The studies indicated that the aqueous extract of Curry leaf protects the rat cardiac tissue against cadmium-induced oxidative stress possibly through its antioxidant activity. As curry leaf is consumed by people as part of their diet in India and South-East Asian and some European countries as well, and, as it has no reported side-effects, the results seem to have relevance at places where humans are exposed to cadmium environmentally or occupationally.

Protective effect of Piper betle leaf extract against cadmium-induced oxidative stress and hepatic dysfunction in rats

The present study was undertaken to examine the attenuative effect of Piper betle leaf extract (PBE) against cadmium (Cd) induced oxidative hepatic dysfunction in the liver of rats. Pre-oral supplementation of PBE (200mg/kg BW) treated rats showed the protective efficacy against Cd induced hepatic oxidative stress. Oral administration of Cd (5mg/kg BW) for four weeks to rats significantly (P>0.05) elevated the level of serum hepatic markers such as serum aspartate transaminase (AST), serum alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), gamma-glutamyl transpeptidase (GGT), bilirubin (TBRNs), oxidative stress markers viz., thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (LOOH), protein carbonyls (PC) and conjugated dienes (CD) and significantly (P>0.05) reduced the enzymatic antioxidants viz., superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), glutathione reductase (GR) and glucose-6-phosphate dehydrogenase (G6PD) and non-enzymatic antioxidants Viz., reduced glutathione (GSH), total sulfhydryls (TSH), vitamin C and vitamin E in the liver. Pre-oral supplementation of PBE (200mg/kg BW) in Cd intoxicated rats, the altered biochemical indices and pathological changes were recovered significantly (P>0.05) which showed ameliorative effect of PBE against Cd induced hepatic oxidative stress. From the above findings, we suggested that the pre-administration of P. betle leaf extract exhibited remarkable protective effects against cadmium-induced oxidative hepatic injury in rats.

Lead and cadmium-induced oxidative stress impacting mycelial growth of Oudemansiella radicata in liquid medium alleviated by microbial siderophores

In this study, the effects of siderophores produced by six bacteria on mycelium growth, Cd and Pb accumulation, lipid peroxidation, protein content and antioxidant enzyme in Oudemansiella radicata were investigated in Cd and Pb-containing liquid medium. The results showed that inoculation with siderophore-containing filtrates (SCF) partly enhanced the growth of O. radicata after 15days, with 0.8-32.4% biomass increase for Cd and 0.7-20.8% for Pb compared to control(s), which lacked siderophore. The maximum enhancement for accumulation were found to be confined to Bacillus sp. FFQ2(s) (26.5%) for Cd and Pseudomonas sp. CY63(s) (158.9%) for Pb. A significant decrease in MDA content indicated that lipid peroxidation in O. radicata was alleviated by siderophores. Besides, antioxidant enzyme SOD and POD activities also displayed obviously decrease in SCF-treated mycelium compared to control(s) treatment, while CAT activity did not present significant change. Protein level in O. radicata treated by SCF increased from 0.3 to 138.0% for Cd and from 10.9 to 107.1% for Pb compared to control(s). Therefore, the present work suggests that microbial siderophores can reduce the toxicity of metals to mycelium and then alleviate heavy metals-inducing oxidative stress in O. radicata.

Cadmium-induced oxidative stress and apoptotic changes in the testis of freshwater crab, Sinopotamon henanense.

Cadmium (Cd), one of the most toxic environmental and industrial pollutants, is known to exert gonadotoxic and spermiotoxic effects. In the present study, we examined the toxic effect of Cd on the testis of freshwater crab, Sinopotamon henanense. Crabs were exposed to different Cd concentrations (from 0 to 116.00 mg·L−1) for 7 d. Oxidative stress and apoptotic changes in the testes were detected. The activities of SOD, GPx and CAT initially increased and subsequently decreased with increasing Cd concentrations, which was accompanied with the increase in malondialdehyde (MDA) and H2O2 content in a concentration-dependent manner. Typical morphological characteristic and physiological changes of apoptosis were observed using a variety of methods (HE staining, AO/EB double fluorescent staining, Transmission Electron Microscope observation and DNA fragmentation analysis), and the activities of caspase-3 and caspase-9 were increased in a concentration-dependent manner after Cd exposure. These results led to the conclusion that Cd could induced oxidative damage as well as apoptosis in the testis, and the apoptotic processes may be mediated via mitochondria-dependent apoptosis pathway by regulating the activities of caspase-3 and caspase-9.

Root adaptations to cadmium-induced oxidative stress contribute to Cd tolerance in the hyperaccumulator Sedum alfredii

Short-term responses of Sedum alfredii roots to Cd exposure was compared in Cd hyperaccumulator (HE) and nonhyperaccumulating ecotype (NHE). Cadmium exposure significantly inhibited root elongation and induced loss of plasma membrane integrity and lipid peroxidation of roots tips in the NHE, whereas these effects were much less pronounced in the HE plants. A strong accumulation of reactive oxygen species with increasing Cd concentration was noted in the NHE root tips, but not in HE. After Cd exposure, a dose-dependent decrease in oxidized glutathione and marked increase in reduced glutathione and non-protein thiols were observed in root tips of HE, but were not seen in the NHE plants. These results suggest that the HE tolerates high Cd in the environment through the differential adaptations against Cd-induced oxidative stress.

Bradykinin potentiating factor isolated from Buthus occitanus venom has a protective effect against cadmium-induced rat liver and kidney damage

Bradykinin and its related peptides are widely distributed in venomous animals, including scorpion. A peptide fraction isolated from the venom of the Egyptian scorpion Buthus occitanus was proved to have a bradykinin-potentiating activity. The aim of the present study was conducted to investigate whether the treatment with bradykinin potentiating factor (BPF) offers more beneficial effects in reversing cadmium-induced oxidative stress in rat liver and kidney. Adult male rats, equally divided into control and two treated groups, 10 animals in each group. group (I) was orally given (1 ml) saline and served as a control group; group (II) of rats was given cadmium chloride (4 mg/kg) alone, once daily an oral dose for 7 successive days; group (III) of rats was given ip injection (1 ml) BPF, once daily a dose for 7 successive days prior to CdCl 2 treatment and on the next 7 successive days with the same dose of cadmium as group II. Both organs were subjected to histopathological analysis with the light microscope. The activities of alanine aminotransferase (ALT), asparate aminotransferase (AST) and alkaline phosphatase (ALP) in serum were measured as indicators of the liver function. As parameters of the kidney function, creatinine, uric acid and urea concentrations in serum were determined. Also, malondialdehyde (MDA), reduced glutathione (GSH), super oxide dismutase (SOD) and catalase (CAT) were determined in both tissues. Cd exposure caused a significant decrease or inhibition in the activities of GSH, SOD, and CAT, with significant increase in the level of MDA, in versus to control groups in both liver and kidney. Also, when Cd was treated in co-administration with BPF induced increase or stimulation in the activity of GSH, SOD, and CAT, with significant decrease in the level of MDA when compared to Cd group in both organs. Histopathological changes of liver and kidney were also in accordance with the biochemical findings. Our data showed that Cd treatment induced histopathological alteration in the liver, severe hydropic degeneration in centrolobular zones. Inflammatory cells infiltration around the congested central vein and an obvious injury in some renal tubules. Bradykinin potentiating factor (BPF) administration prevented the histopathological alterations which observed in Cd-groups and both liver and kidney had essentially normal appearance in histopathological examination. In conclusion, BPF markedly ameliorated cadmium-induced liver and kidney tissue damage as evidenced by histological and biochemical examinations and acts as a potent scavenger of free radicals to protect the liver and kidney against the deleterious effect of acute cadmium intoxication.

Mechanisms underlying the protective effect of zinc and selenium against cadmium-induced oxidative stress in zebrafish Danio rerio

The present study was designed to elucidate the protective effect mechanism of Zinc (Zn) and Selenium (Se) on cadmium (Cd)-induced oxidative stress in zebrafish. For this purpose we investigate the response of oxidative stress markers, metallothionein accumulation and gene expression in liver and ovary of female zebrafish exposed to 0,4mg/l Cd in water and supplemented with Zn (5mg kg(-1)) and/or Se (2mg kg(-1)) for 21days in their diet. Liver and ovary Cd uptake was evaluated after the exposure period. Cd exposure significantly inhibited the antioxidant enzyme activities termed as catalase (CAT), superoxide dismutase (SOD) and glutathione peroxydase (GPx) and caused a pronounced malondialdehyde (MDA) accumulation in both organs. Co-administration of Zn and Se reversed the Cd-induced toxicity in liver and ovary measured as MDA accumulation. Interestingly, gene expression patterns of Cat, CuZnSod and Gpx were up-regulated when related enzymatic activities were altered. Zebrafish metallothionein transcripts (zMt) significantly decreased in tissues of fish supplemented with Zn and/or Se when compared to Cd-exposed fish. Our data would suggest that Zn and Se protective mechanism against Cd-induced oxidative stress is more depending on the correction of the proteins biological activities rather than on the transcriptional level of related genes.

Connexin43 Hemichannels Contribute to Cadmium-Induced Oxidative Stress and Cell Injury

We investigated the potential involvement of connexin hemichannels in cadmium ions (Cd(2+))-elicited cell injury. Transfection of LLC-PK1 cells with a wild-type connexin43 (Cx43) sensitized them to Cd(2+)-elicited cell injury. The cell susceptibility to Cd(2+) was increased by depletion of glutathione (GSH) with DL-buthionine-[S,R]-sulfoximine, and decreased by N-acetyl-cysteine or glutathione reduced ethyl ester. Fibroblasts derived from Cx43 wild-type (Cx43+/+) and knockout (Cx43-/-) fetal littermates displayed different susceptibility to Cd(2+). Cd(2+) induced a higher concentration of reactive oxygen species, a stronger activation c-Jun N-terminal kinase, and significantly more severe cell injury in Cx43+/+ fibroblasts, as compared with Cx43-/- fibroblasts. Cd(2+) caused a reduction in intracellular GSH, whereas it elevated extracellular GSH. This effect of Cd(2+) was more dramatic in Cx43+/+ than Cx43-/- fibroblasts. Treatment of Cx43+/+ fibroblasts with Cd(2+) caused a Cx43 hemichannel-dependent influx of Lucifer Yellow and efflux of ATP. Collectively, our study demonstrates that Cx43 sensitizes cells to Cd(2+)-initiated cytotoxicity, possibly through hemichannel-mediated effects on intracellular oxidative status.