镉暴露致大鼠肾损伤的量效关系及其机制

doi:10.3969/j.issn.1004-616x.2016.06.007

Abstract

Abstract: OBJECTIVE: This study was designed to investigate the dose-dependent relationship and the possible mechanisms of renal injury by cadmium in rats. METHODS: Forty male rats were randomly divided into four groups (0,1,3 and 5 mg/kg CdCl₂) groups. The rats were intra-gastrically administrated CdCl₂ daily to investigate the induction of renal injury. Blood urea nitrogen (BUN) and serum creatinine (SCr) were measured to evaluate renal function. Kidney tissues were stained with hematoxylin-eosin (HE) and observed for histopathological changes. Transmission electron microscopye was used to detect ultrastructural abnormalities. Levels of ROS in kidney was detected by DHE and MitoSOX staining. The levels of SOD1,SOD2,GPx-1,CAT,Bax,Bcl-2,GRP78 were measured by Western blotting. RESULTS: After exposure to CdCl₂ for 4 weeks,the relative kidney weights showed no significant difference among the 4 groups. As the dose of CdCl₂ increased,the levels of BUN elevated gradually (r=0.463,P<0.05). Pathological damages to kidneys were progressively aggravated. Swelling of glomerulus and renal tubule,and necrosis of tubular epithelial cells were observed under light microscopy. And it was also observed that the lumina of renal tubules contained necrotic epithelial cellular debris and casts. Interstitial hyperemia and inflammatory infiltration were found as well. The ultrastructure of mitochondria in the epithelium of proximal convoluted tubule showed swelling,deformation and vacuolation in a dose-dependent manner. The level of kidney ROS elevated gradually. Levels of SOD2,GPx-1 and CAT were upregulated (r=0.854,0.975,0.918,P all<0.05) while SOD1 were downregulated (r=-0.987,P<0.05) as the dose of CdCl₂ increased. Meanwhile,levels of the apoptosis-promoting Bax increased (r=0.226,P<0.05) while the anti- apoptotic Bcl-2 decreased (r=-0.85,P<0.05) and the ratio of Bax/Bcl-2 increased (r=0.83,P<0.05). The levels of GRP78 also increased when the dose of CdCl₂ increased (r=0.913,P<0.05). CONCLUSION: The results demonstrate that there was a dose-dependent toxic effect of CdCl₂ on renal structure and function. Moreover,oxidative stress might be the key mechanism involved in the toxicity of cadmium because of increased antioxidase expression and levels of ROS.

Key words: cadmium exposure, renal injury, dose-dependent, oxidative stress, reactive oxygen species

CLC Number:

R994.6

WANG Lele, LIU Jiangzheng, LIU Mengmeng, KONG Deqin, ZHANG Tao, YU Weihua, LIU Rui, ZHANG Xiaodi, WANG Xin, HAI Chunxu. Dose-dependent induction of renal injury by cadmium in rats[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2016, 28(6): 446-452.

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Dose-dependent induction of renal injury by cadmium in rats

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