水飞蓟宾对顺铂所致大鼠肾毒性的预防作用

Effectof silibinin on nephrotoxicity induced by cis-diammine- dichloroplatinum in rats

观察了大鼠 ig水飞蓟宾 (SB)对顺铂 (CDDP)肾毒性的预防作用及可能机理 ,并初步探讨 SB对CDDP抗肿瘤效应的影响 .大鼠经 ig SB 2 0 0 mg·kg-1后 1 h,ip CDDP5mg· kg-13和 5d后与仅ip CDDP组比较 ,体重和谷胱甘肽过氧化物酶活性明显升高 ,而尿素氮含量 ,尿 N -乙酰 -β- D-氨基葡萄糖苷酶的排泄及丙二醛生成均明显降低 .ig SB30 0 mg· kg-1后 ip CDDP5mg·kg-1对荷 S180 小鼠的瘤重抑制率为 85.7% ,与仅 ip CDDP 5mg· kg-1组的瘤重抑制率 (81 .7% )无明显差别 ,ig SB30 0mg·kg-1组的瘤重抑制率为 30 % .表明 SB明显预防 CDDP所致大鼠肾毒性 ,但不影响 CDDP抗肿瘤作用 . SB预防肾毒性的部分机理可能与清除自由基 ,抑制脂质过氧化形成 ,并提高机体抗氧化能力有关 .SB对 CDDP抑制小鼠 S180

The protective effect of silibinin (SB) on nephrotoxicity of cis- diamminedich- loroplatinum(CDDP) ,its possible mecha- nism and influence of SB on antitumor activ- ity of CDDP were investigated. For rats pretreated with SB(2 0 0 mg· kg- 1 ,ig) be- fore giving CDDP (5 mg· kg- 1 ,ip) ,the changes in body weight and activity of mito- chondrial glutathione peroxidase were sig- nificantly increased,but blood urea nitro- gen level,urinary N- acetyl- β- D- glu- cosaminidase excretion and formation ofmalondialdehyde were significantly de- creased. The rate of inhibition of tumor weight of mice(85 .7% ) pretreated with SB (30 0 mg·kg- 1 ,ig) before giving CDDP(5 mg· kg- 1 ,ip) was not different from that(81 .7% ) of mice given CDDP(5 mg· kg- 1 ,ip) alone.The inhibition rate of tu- mor weight of mice treated with SB(30 0 mg · kg- 1 ,ig) alone was30 % .The results showed that SB pretreatment can ameliorate the nephrotoxicity of CDDP to rats. The possible mechanisms that SB alleviate the nephrotoxicity of CDDP are the scaven- gation of free radicals,the depression of lipid peroxidation and the strength of an- tioxidant ability. SB pretreatment would not reduce the antitumor activity of CDDP on S1 80 ,and SB itself may possess some an- titumor activity.