姜黄素对顺铂所致大鼠肾毒性的防护作用

Preventive effects of curcumin on cisplatin-induced nephrotoxicity in rats

目的研究姜黄素(CMN)对顺铂(CDDP)所致肾损害的防护作用,并探讨其可能机制。方法将42只大鼠按体重随机分6组,分别为对照组、CMN组、CDDP组、CMN(204、0和80 mg/kg)+CDDP组。CMN连续给予大鼠灌胃3 d,第2天灌胃后1 h腹腔注射CDDP(5.5 mg/kg)。CDDP处理后,分别在第1、3和5天采血,测定血清尿素氮(BUN)和肌酐(CRE)。第5天采血后处死动物,测定肾脏系数、肾皮质匀浆丙二醛(MDA)、谷胱甘肽(GSH)含量和谷胱甘肽过氧化物酶(GSH-Px)活力以及肾组织铂(Pt)含量等。同时利用体外实验观察对抗增殖作用的影响。结果CMN预处理可减轻CDDP引起的肾脏系数升高及BUN、CRE水平升高;能抑制CDDP引起的MDA形成增高;并能提升CDDP引起的GSH含量和GSH-Px活力下降。CMN低剂量的上述作用明显(P<0.05或P<0.01)。CMN防护组与CDDP组的人卵巢癌细胞系和膀胱癌细胞系的半数抑制浓度差异无显著性。结论CMN经口给予能防护CDDP所致的肾损害,其机制可能与其抗氧化作用和清除自由基活性有密切关系。较高剂量CMN未见防护CDDP所致肾毒性的作用,其原因可能与其助氧化作用有关。CMN对CDDP抗肿瘤细胞增殖作用无明显影响。

Objective To investigate the protective effect of curcumin （CMN） on cisplatin （CDDP）-induced nephrotoxicity in rats and plausible mechanism.Methods Female Sprague-Dawhy rats were randomly divided into 6 groups according to their weights （7 rats in each）. Animals received CMN by gavage for 3 days, and after 1 h of the second administration of CMC. Animals were intraperitoneally administration of CDDP （5.5 mg/kg）. Blood urea nitrogen （BUN） and creatinine （CRE） were determined on 1,3,5 days after CDDP treatment. All animals were killed and kidney were analyzed for malondialdehyde （MDA）, glutathion （GSH）, glutathione peroxidase （GSH-Px） and platinum on 5 days after CDDP treatment. Moreover, the effects of CMN on the antipreliferative activity of CDDP were measured in vitro. Results CMN pretreatment at lower doses would alleviate the CDDP-induced increases of BUN, CRE, and inhibit the increases of MDA formation in kidney cortex homogenate, and enhance the decreases of contents of GSH and activities of GSH-Px in kidney cortex homogenate in rats. The alleviation of CMN on CDDP-induced nephrotoxicity and oxidative stress were not observed at higher doses of CMN. Additionally, significant effects of CMN treatment on antipreliferation of CDDP for human urothelial carcinoma cell line SCaBER and human ovarian carcinoma cell line HO-8910PM cells were not found. Conclusion By oral administration, CMN pretreatrnent at lower doses can remarkably alleviate CDDP-induced nephrotoxicity. The mechanisms may be involved in antioxidation, scanvaging of free radicals. CMN at higher doses would be a co-oxidant and not protect against CDDP-induced nephretoxicity and oxidative stress. Moreover, CMN does not influence anti-proliferation of CDDP on tumor cells.