| ObjectiveCadmium (Cd) is a kind of toxic heavy metals with a biological half-life of about 10 ~ 30 years. It is the known toxicant that accumulates most easily in both humans and experimental animals. The kidney is the most important target where Cd accumulates, and Cd exposure can mainly damage the renal tubular epithelial cells. Many studies have shown that oxidative stress appears to play a major role in Cd-induced toxicity since Cd can induce oxidative injuries in many tissues by lipid peroxidation or by inhibition of components of the antioxidant defense system. Cd-induced nephrotoxicity is believed to be irreversible at advanced stages and no effective treatment is currently available. The molecular mechanism of Cd-induced nephrotoxicity is yet unclear.The aim of the present study was to analyze the oxidative injuries induced by Cd with different doses in the Sprague-Dawley (SD) rats in order to find out the dose-effect relationship of oxidative injuries induced by Cd and consequently provide basic data for further studying Cd toxicity. The Cd-induced toxicity animal model in this study had been established by chronically injecting rats with CdCl2 and by consequently treating intraperitoneally (ip) them with either Glu-tathione (GSH) , Vitamin C (Vit-C) or2,3-dimercapto-l-propanesulfonic sodium (DMPS) in order to study the effects of them on the nephrotoxicity induced by Cd and therefore provide the foundation for prevention and treatment of Cd-induced toxicity. The effects of Cd on the cell cycle, apoptosis and expression of Bcl-2 of renal cells in mice were discussed, and the characteristics of them were elucidated. Therefore, this could offer the important data for further discussing the molecular mechanisms of the toxicity induced by Cd.Methods1. The study of the dose-effect relationship of oxidative injuries induced by Cd in ratsForty-eight male and female SD rats, 100 50 g of weight, were purchased from Laboratory Animal Center in China Medical University. The animals were housed at 17 ~23 C , and they were given unlimited access to rat chow and water. The rat chow was provided by Laboratory Animal Center. The animals were fed for seven days before experiment, and then they were divided randomly into four groups: the control group and three Cd groups. Three Cd groups rats were injected subcutaneously (sc) with 2.5, 5.0, 10. 0 mol CdCl2/ kg per day respectively , and another group rats were injected sc with saline per day as a control , five times per week, for eight weeks. After the 9th week, the animals were housed individually in metabolic cages for 24 hours and the urine samples were collected over ice. Blood samples were collected by puncturing into abdominal aorta under ether anesthesia. Then all the animals were killed, and the liver and kidney were collected. The liver, renal cortex, blood and urine samples were used for biochemical analysis. Cd contents in the liver, renal cortex, blood and urine samples were measured. GSH contents in the liver and renal cortex and Glutathione-peroxidase (GSH-Px) activities, Malondialdehyde (MDA) contents in the liver, renal cortex and blood samples were also measured. All indicators were analyzed in freshly collected samples from selected groups.2. The effects of GSH, Vit-C and DMPS on nephrotoxicity induced by Cd Fifty male and female SD rats, 100 50 g of weight, were purchased from Laboratory Animal Center in China Medical University. The animals were fed for seven days before experiment, and then they were divided randomly into five groups: the control group and four experimental groups. Four experimental groups of ten animals each received sc injection of 5. 0 mol CdCl2/ kg per day, and each of the control group was injected sc with saline per day, five times per week, for up to eleven weeks. By the end of Week 11, the animals were housed individually in metabolic cages for 24 hours and the urine samples were collectedover ice. Then the animals of four Cd groups received ip treatment of either saline, 1.0mmol GSH/kg, 4.0mmol Vi...
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