Effects of Selenium with Vitamin E and Melatonin on Cadmium-Induced Oxidative Damage in Rat Liver and Kidneys

The present study was performed to determine the protective effects of melatonin alone and vitamin E with selenium combination against cadmium-induced oxidative damage in rat liver. A total of 60 male rats were equally divided into five groups, one of which acted as control receiving subcutaneous injections of physiological saline. The remaining four groups were treated with subcutaneous injections of cadmium chloride at a dose of 1 mg/kg weight. The first study group received no treatment. The second group was treated with a combination of 60 mg/kg vitamin E and 1 mg/kg sodium selenite. Group 3 was treated with 10 mg/kg melatonin, and the four group received a combination of vitamin E, sodium selenite, and melatonin at the doses mentioned above. After 1 month, the animals were killed, and liver and kidneys were excised for histopathological inspection and determination of tissue malondialdehyde and the activity of superoxide dismutase. The animals receiving no treatment showed significantly higher malondialdehyde levels and reduced activity of superoxide dismutase (p < 0.05). Treatment with antioxidants resulted in a significant reduction in malondialdehyde when compared to nontreated animals (p < 0.05) and increase in the enzyme activity that was almost the same as the controls. The pathological findings were also in parallel with the results of the biochemical analysis. In conclusion, all the agents tested had protective effects against cadmium-induced oxidative damage.     

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.     

Protective Effects of Onion Extract on Cadmium-Induced Oxidative Stress,Histological Damage,and Apoptosis in Rat Heart

To date, there is no available information on the protective effect of onion (Allium cepa) extract (AcE) on cadmium (Cd)-induced cardiotoxicity. The present study was performed to assess the possible antioxidant and anti-apoptotic roles of AcE in Cd-induced cardiotoxicity in rats. A Cd group was injected subcutaneously with CdCl₂ dissolved in saline at a dose of 2 ml/kg/day for 30 days, resulting in a dosage of 1 mg/kg Cd. The rats in the AcE-treated group were given 1 ml of AcE via intragastric intubation for 30 days. The rats intoxicated with Cd for 30 days showed increased tissue malondialdehyde (MDA) levels and decreased levels of the enzymatic antioxidants superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) in cardiac tissue. AcE attenuated these adverse effects of Cd. After Cd exposure, histological abnormalities were observed, including myofibrillar loss, vacuolization of cytoplasm and irregularity of myofibrils. These histological alterations were effectively attenuated by the treatment with AcE. Furthermore, our data indicate a significant reduction of apoptosis in the cardiomyocytes of the Cd group treated with AcE therapy. Animal studies show antioxidant effects of AcE. But to date, no study reported the effect of AcE on biochemical and histopathological changes due to Cd induced on rat heart. Our study showed that AcE therapy reduced Cd-induced oxidative stress and apoptosis, possibly through its antioxidant and anti-apoptotic activity.     

Protective Effect of Agaricus blazei Polysaccharide Against Cadmium-Induced Damage on the Testis of Chicken

Biological Trace Element Research - Cadmium (Cd) exposure can cause reproductive toxicity through oxidative stress and inflammatory response. A polysaccharide extract of the edible mushroom...     

Ameliorative Effects of Selenium on Cadmium-Induced Injury in the Chicken Ovary: Mechanisms of Oxidative Stress and Endoplasmic Reticulum Stress in Cadmium-Induced Apoptosis

Despite the well-established toxicity of cadmium (Cd) to animals and the ameliorative effects of selenium (Se), some specific mechanisms in the chicken ovary are not yet clarified. To explore the mechanism by which the toxicity effect of Cd is induced and explore the effect of supranutritional Se on Cd toxicity in female bird reproduction, forty-eight 50-day-old Isa Brown female chickens were divided randomly into four groups. Group I (control group) was fed the basic diet containing 0.2 mg/kg Se. Group II (Se-treated group) was fed the basic diet supplemented with sodium selenite (Na₂SeO₃), and the total Se content was 2 mg/kg. Group III (Se + Cd-treated group) was fed the basic diet supplemented with Na₂SeO₃; the total Se content was 2 mg/kg, and it was supplemented with 150 mg/kg cadmium chloride (CdCl₂). Group IV (Cd-treated group) was with the basic diet supplemented with 150 mg/kg CdCl₂. The Cd, estradiol (E2), and progestogen (P4) contents changed after subchronic Cd exposure in chicken ovarian tissue; subsequently, oxidative stress occurred and activated the endoplasmic reticulum (ER) pathway to induce apoptosis. Further, Se decreased the accumulation of Cd in ovarian tissue, increased the E2 and P4 contents, alleviated oxidative stress, and reduced apoptosis via the ER stress pathway. The present results demonstrated that Cd could induce apoptosis via the ER stress pathway in chicken ovarian tissue and that Se had a significant antagonistic effect. These results are potentially valuable for finding a strategy to prevent Cd poisoning.     

Effects of Oxidative Stress on Immunosuppression Induced by Selenium Deficiency in Chickens

Selenium (Se) is an important nutritional trace element possessing immune-stimulatory properties. The aim of this 75-day study was to investigate effect of oxidative stress on immunosuppression induced by selenium deficiency by determining antioxidative function, morphological changes, DNA damage, and immune function in immune organ of chickens. One hundred sixty 1-day-old chickens (egg-type birds) were randomly assigned to two groups of 80 each and were fed on a low-Se diet (0.032?mg/kg Se) or a control diet (0.282?mg/kg Se, sodium selenite), respectively. Se contents in blood and immune organ (thymus, spleen, bursa of Fabricius) were determined on days 30, 45, 60, and 75, respectively. Antioxidative function was examined by total antioxidant capacity (T-AOC), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and xanthine oxidase (XOD), and oxidative damage was examined by malondialdehyde (MDA) detection. DNA damage was measured by comet assay, and immune function was examined by determining serum interleukin-1?? (IL-1??), interleukin-2 (IL-2), and tumor necrosis factor (TNF) contents. The results showed that Se concentrations in the low-Se group were significantly lower (P?<?0.05) than in the control group. Low-Se diet caused a decrease in the activities of T-AOC, SOD, GSH-Px, and an increase in XOD activity and MDA content. Pathological lesions and DNA damage of immune tissues were observed in low-Se group, while the serum IL-1?? and IL-2 contents decreased, and TNF content increased. The present study demonstrated that chickens fed deficient in Se diets exhibited lesions in immune organs, decreased serum IL-1??, IL-2 content, and serum TNF content, indicating that oxidative stress inhibited the development of immune organs and finally impaired the immune function of chickens.     

Cadmium-Induced Oxidative Stress in the Rat Testes: Protective Effects of Betaine

The aim of the present study was to evaluate the antioxidant effects of betaine against oxidative stress and pathological changes mediated by cadmium in the testes of rats. The adult male Wistar rats were allocated into three experimental groups as follows: the cadmium group received cadmium chloride at the dosage of 2 mg/kg intraperitoneally thereafter, the rats treated by physiological saline for 10 consecutive days. The betaine plus cadmium group received betaine at the dosage of 1.5 % w/w of the total diet orally for 10 consecutive days and cadmium chloride injected at the 2nd day of the betaine treatment. The control rats were injected physiological saline. Both testes of rats were removed for antioxidant assay and pathological changes evaluation on days 5 and 10 after cadmium toxicity. TBARS concentration (as a lipid peroxidation marker) was significantly higher in the cadmium group by day 10 compared to control and betaine plus cadmium groups, and it was significantly higher in cadmium group by day 5 in comparison with the controls. Catalase (CAT) and glutathione peroxidase activities decreased significantly by day 10 in cadmium group when compared to the controls. In contrast, CAT and superoxide dismutase activities increased significantly by day 10 in betaine plus cadmium group when compared to the cadmium group. In addition, the antioxidant effects of betaine could prevent testicular pathological changes in betaine plus cadmium group. The present data allow us to exploit the advantages of this nutrient agent in future studies.     

Protective Roles of Selenium on Nitric Oxide-Mediated Apoptosis of Immune Organs Induced by Cadmium in Chickens

Little is known about the influence of subchronic cadmium exposure on apoptosis in the immune organs of birds and the protective effects on apoptosis by selenium against cadmium. The aim of this study was to investigate the effect of subchronic cadmium exposure on nitric oxide and apoptosis in the immune organs of chicken and the protective roles of selenium against cadmium-induced apoptosis. Two hundred ten 30-day-old chickens were randomly assigned to three groups and were fed a basal diet, cadmium?+?selenium (as 150 mg of CdCl₂ per kg of diet?+?10 mg of Na₂SeO₃ per kg of diet ) or cadmium (as 150 mg of CdCl₂ per kg of diet) in basic diets for 15, 30, 45, and 60 days. Then, the production of nitric oxide, messenger RNA (mRNA level), and the activity of inducible nitric oxide synthase, ultrastructural changes, TUNEL assay, and flow cytometric analysis of apoptosis and Bcl-2 and p53 mRNA levels in the immune organs were examined. The results showed that cadmium exposure caused ultrastructural damage and increased production of nitric oxide, mRNA level, and activity of inducible nitric oxide synthase, the degree, and the number of apoptotic cells in a time-dependent manner. Cadmium exposure decreased Bcl-2 mRNA level and increased p53 mRNA level in a time-dependent manner. Selenium supplementation during dietary cadmium reduced the production of nitric oxide, the mRNA level, and activity of inducible nitric oxide synthase, ultrastructural damage, and apoptosis in the immune organs of chicken. It indicated that cadmium induced nitric oxide-mediated apoptosis of immune organs, and selenium played protective effects against cadmium-induced apoptosis in the immune organs of chickens.     

Protective Effects of ACY-1215 Against Chemotherapy-Related Cognitive Impairment and Brain Damage in Mice

Neurochemical Research - Chemotherapy-related cognitive impairment (CRCI) is a potential long-term side effect during cancer treatment. There are currently no effective treatments for CRCI....     

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.     

Selenium Mitigates Cadmium-Induced Adverse Effects on Trace Elements and Amino Acids Profiles in Chicken Pectoral Muscles

Biological Trace Element Research - Cadmium (Cd), as one of the most toxic heavy metals, has become a widespread environmental contaminant and threats the food quality and safety. The protective...     

The Antagonistic Effect of Selenium on Cadmium-Induced Damage and mRNA Levels of Selenoprotein Genes and Inflammatory Factors in Chicken Kidney Tissue

Selenium (Se) is a necessary trace mineral in the diet of humans and animals. Cadmium (Cd) is a toxic heavy metal that can damage animal organs, especially the kidneys. Antagonistic interactions between Se and Cd have been reported in previous studies. However, little is known about the effects of Se against Cd toxicity and on the mRNA levels of 25 selenoprotein genes and inflammatory factors in chicken kidneys. In the current study, we fed chickens with a Se-treated, Cd-treated, or Se/Cd treated diet for 90 days. We then analyzed the mRNA expression of inflammatory factors (including prostaglandin E synthase (PTGES), nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α), and cyclooxygenase-2 (COX-2)) and 25 selenoprotein genes (Gpx1, Gpx2, Gpx3, Gpx4, Txnrd1, Txnrd2, Txnrd3, Dio1, Dio2, Dio3, SPS2, Sepp1, SelPb, Sep15, Selh, Seli, Selm, Selo, Sels, Sepx1, Selu, Selk, Selw, Seln, Selt). The results demonstrated that Cd exposure increased the Cd content in the chicken kidneys, renal tubular epithelial cells underwent denaturation and necrosis, and the tubules became narrow or disappeared. However, Se supplementation reduced the Cd content in chicken kidneys and induced normal development of renal tubular epithelial cells. In addition, we also observed that Se alleviated the Cd-induced increase in the mRNA levels of inflammatory factors and ameliorated the Cd-induced downtrend in the mRNA levels of 25 selenoprotein genes in chicken kidneys.     

Protective Role of Glutathione Synthesis on Radiation-Induced DNA Damage in Rabbit Brain

1. Radiotherapy has attracted increasing interest in recent years. It is known that ionizing radiation induces oxygen radical injury, whereas oxidative stress by the radiation can cause cellular responses to defense cellular injury. In this study, the metabolism of antioxidants in response to ionizing radiation to the brain was studied in the brain using experimental rabbits.2. Ionizing radiation to the hemicerebrum caused an increase in the levels of glutathione (GSH) and the activity of a GSH synthesizing enzyme, -glutamylcysteine synthetase (-GCS), and Cu,Zn-superoxide dismutase (Cu,Zn-SOD). Ionizing radiation also induced DNA-damage estimated by the formation of 8-hydroxydeoxyguanosine. These changes were dependent on the radiation dose.3. Previous intrathecal-administration of buthionine sulfoximine (100 M), a specific inhibitor of -GCS, increased DNA damage by radiation in the radiated hemicerebrum. That of S-methyl GSH, on the other hand, resulted in a significant reduction of DNA damage by radiation.4. These results suggest that synthesis of GSH and Cu,Zn-SOD is responsive to ionizing radiation and this induction of antioxidants may play a role in reducing tissue damage in radiotherapy.     

Mechanism Underlying the Protective Effect of Selenium on NO-Induced Oxidative Damage in Bovine Mammary Epithelial Cells

This experiment was conducted to investigate the effects and mechanism of selenium (Se) on antioxidant and immune function of bovine mammary epithelial cells (BMEC) damaged by nitric oxide (NO). The third-generation BMEC was randomly divided into eight treatments with six replicates. The BMEC in the control group was cultured in the medium without Se and diethylenetriamine/NO (DETA/NO) for 30 h. For the DETA/NO group and Se protection group BMEC were exposed to different concentrations of Se (0, 10, 20, 50, 100, 150, and 200 nmol/L) for 24 h, followed by treatment with DETA/NO (1000 μmol/L) for 6 h. Compared with the control group, DETA/NO decreased proliferation rate and activity of thioredoxin reductase (TrxR; P < 0.05). Additionally, DETA/NO decreased the gene expression of both nuclear factor-E2-related factor 2 (Nrf2) and TrxR, as well as the protein expression level of TrxR. However, the activity, and expression levels of inducible nitric oxide synthase (iNOS), as well as the concentration and gene expression level of interleukin-1β (IL-1β) and the concentration of NO significantly increased (P < 0.05). The gene expression levels of indexes related to the mitogen-activated protein kinase (MAPK) signaling pathway showed similar changes. Treatment of BMEC with Se significantly reversed DETA/NO-induced changes in a linear or quadratic dose-dependent manner (P < 0.05), with greatest benefit at 50 nmol/L. These data suggests that Se improves the antioxidant function of BMEC, and protects cells from DETA/NO-induced oxidative damage, primarily by enhancing the activity of TrxR and decreasing the concentration of NO through modulation of Nrf2 and MAPK signaling pathways.

     

Cadmium-Induced Injury and the Ameliorative Effects of Selenium on Chicken Splenic Lymphocytes: Mechanisms of Oxidative Stress and Apoptosis

Cadmium (Cd) is an important environmental pollutant present in soil, water, air, and food. Selenium (Se) can antagonize some metal element toxicity including Cd. To investigate the cytotoxicity of Cd and the protective effects of Se on bird immunocytes in vitro, chicken splenic lymphocytes with CdCl₂ (10^?6 mol/L), Na₂SeO₃ (10^?7 mol/L), and the mixture (10^?7 mol/L Na₂SeO₃ and 10^?6 mol/L CdCI₂) were incubated for 12, 24, 36, and 48 h, respectively. A high level of malondialdehyde (MDA) and reactive oxygen species (ROS) productions were observed in Cd treatment group; the activities of catalase (CAT), glutathione peroxidise (GSH-Px), superoxide dismutase (SOD), and the mitochondrial inner transmembrane potential (ΔΨm) were significantly lower in Cd treatment group than those in controls (P?P?mRNA level of Bak, p53, caspase-3, caspase-9, and cytochrome c (Cyt c) and decreased Bcl-2, Bcl-xl, and CaM were observed in Cd treatment group. Se ameliorated ΔΨm and [Ca²⁺]i for mitochondria function restoring, and Se was able to modulate the expression of relative genes. In conclusion, concurrent treatment with Se reduced the Cd-induced morphological changes and oxidative stress, ion disorder, and apoptosis, suggesting that the toxic effects of Cd on the chicken splenic lymphocytes were partly meliorated by Se.     

Effects on Liver Hydrogen Peroxide Metabolism Induced by Dietary Selenium Deficiency or Excess in Chickens

To determine the relationship between dietary selenium (Se) deficiency or excess and liver hydrogen peroxide (H₂O₂) metabolism in chickens, 1-day-old chickens received insufficient Se (0.028 mg Se per kg of diet) or excess Se (3.0 or 5.0 mg Se per kg of diet) in their diets for 8 weeks. Body and liver weight changes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, H₂O₂ content, and activities and mRNA levels of enzymes associated with H₂O₂ metabolism (catalase (CAT) and superoxide dismutase (SOD) 1–3) were determined in the liver. This study showed that Se deficiency or excess Se intake elicited relative severe changes. Se deficiency decreased growth, while Se excess promoted growth in chickens. Both diets vastly altered the liver function, but no obvious histopathological changes were observed in the liver. Se deficiency significantly lowered SOD and CAT activities, and the H₂O₂ content in the liver and serum increased. Se excess (3.0 mg/kg) decreased SOD and CAT activities with changes in their mRNA levels, and the H₂O₂ content increased. The larger Se excess (5.0 mg/kg) showed more serious effects but was not fatal. These results indicated that the H₂O₂ metabolism played a destructive role in the changes in bird liver function induced by Se deficiency or excess.     

Protective Effects of Selenium on Cyclophosphamide-Induced Oxidative Stress and Kidney Injury

Cyclophosphamide (CP) is a common anticancer drug, but its use in cancer treatment is limited due to its severe toxicities induced mainly by oxidative stress in normal cells. Reactive oxygen species (ROS) lead to multiple organ injuries, including the kidneys. Selenium (Se) is a nutritionally essential trace element with antioxidant properties. In the present study, the possible protective effect of Se on CP-induced acute nephrotoxicity was investigated. Forty-two Sprague-Dawley rats were equally divided into six groups of seven rats in each. The control group received saline, and other groups were injected with CP (150 mg/kg), Se (0.5 or 1 mg/kg), or CP + Se intraperitoneally. Total antioxidant capacity (TAC), total oxidant state (TOS), oxidative stress index (OSI), creatinine, and cystatin C (Cys C) levels were measured in the sera. In addition, kidney tissues were examined histologically. In the CP alone treated rats, creatinine, Cys C, TOS, and OSI levels increased, while TAC level decreased. CP-induced histological damages were decreased by co-treatment of Se and biochemical results supported the microscopic observations. In conclusion, our study points to the therapeutic potential of Se and indicates a significant role of ROS in CP-induced kidney toxicity.     

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

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