葡甲胺对顺铂所致大鼠肾毒性的预防作用

目的　研究葡甲胺 (N MG)对顺铂 (CDDP)所致大鼠肾毒性的预防作用及其可能机制。方法　大鼠1次腹腔注射 5mg/kgCDDP动物模型 ,于CDDP处理前 1h经口给予N MG预处理。检测指标包括血尿素氮BUN、尿蛋白、尿铂 (Pt) ,肾组织匀浆中NOS、NO、MDA、SOD及肾组织Pt含量 ,同时观察抗肿瘤活性。结果　给药后第 3、5天N MG预处理组可明显预防CDDP所致大鼠肾功能损害 ,降低肾组织中NOS、NO、及MDA含量 ,增加SOD活性 (P <0 0 5或P <0 0 1)。另外 ,给药后第 3天尿Pt(0 .42 5 μg/mgCr)排泄量非常显著地高于CDDP组(0 2 45 μg/mgCr,P <0 0 1) ,肾组织Pt含量于给药后第 3、5天显著低于CDDP组 (P <0 0 5 )。N MG预处理对荷瘤小鼠的肿瘤抑制率与CDDP组无显著性差异。结论　N MG预处理能明显预防CDDP所致大鼠的肾损害 ,其预防作用机制可能是N MG促进Pt经尿排出 ,并减少了肾组织Pt蓄积 ,从而CDDP产生的自由基减少 ,脂质过氧化程度减轻。N MG对CDDP抗肿瘤活性无明显影响。

Preventive effect of N-methyl-D-glucamine against cisplatin nephrotoxicity in Rats

Objective To investigate the protective effect of N methyl glucamine(N MG)on Cisplatin(CDDP) induced nephrotoxicity in rats and its possible mechanism.Methods Male Sprague Dauley rats were injected i.p.with 5 mg/kg CDDP combined with 2 g/kg N MG given i.g 1 hour before the adminstration of CDDP.BUN,Urinary protein and platinum contents were determined.Kidneys were analyzed for NOS,NO,MDA,SOD and platinum on 3,5 and 7 days after treatment.Moreover,the effect of N MG on the antineoplastic activity of CDDP was measured in mice bearing S 180 .Results N MG alleviated nephrotoxicity induced by cisplatin on day 3 and 5 after administration of CDDP.At the same time,NOS,NO and MDA contents decreased and SOD activities restored ( P<0 05 or P<0 01 ).The excretion evels of urinary platinum increased significantly on day 3 after treatment( P< 0 01),while renal platinum contents decreased on both day 3 and 5.The combination of CDDP and N MG didn't influence the inlibition tumor,action of CDDP.Conclusion These results indicated that N MG was useful for prevention of renal damage induced by CDDP.N MG mediated protection might be related to a reduced exposure of the renal tissue to platinum during the course of its enhanced excretion.As a result,free radicals induced by CDDP were decreased and the extent of lipid peroxidation was ameliorated in rat kidneys.Moreover,the combination of CDDP and N MG would not interfere with the antitumor action of CDDP for S 180 sarcoma.