Protective Effects Of Astragalus Membranaceus On The Cisplatin-Induced Kidney Damage In Rats

Objective Cisplatin(cis-diamminedichloroplatinum,CDDP)is an effective chemotherapeutics which has been widely used currently.However,it also brings about many serious side effects such as symptoms of alimentary tract, ototoxicity,bone marrow suppression,hepatotoxicity and especially nephrotoxicity.Astragalus membranaceus has many pharmacologic activity such as anti-oxidative,anti-inflammatory and anti-tumor et al with low toxicity.In this study,we observed and researched the protective effects of Astragalus membranaceus on the cisplatin-induced kidney damage in rats,and attempted to provid some significant experimental bases for the prevention of nephrotoxicity in cisplatin-treated patients.Methods Female adult Sprague-Dawley rats(180-200g)were randomly divided into five groups(seven rats in each groups).Each group was treated as the follows:ⅠControl group:animals were received 1.5ml NS from the day 1 to day 7 by injection of the abdomen(ip);ⅡCDDP group:animals were received 1.5ml NS from the day 1 to day 7 by injection of the abdomen(ip)and were received 6mg/kg CDDP by injection of the abdomen(ip)on the day 3;Ⅲ6g/kg AM before CDDP group:animals were received 6g/kg AM from the day 1 to day 7 by injection of the abdomen(ip),and were received 6mg/kg CDDP by injection of the abdomen(ip)on the day 3.Ⅳ12g/kg AM before CDDP group: animals were received 12g/kg AM from the day 1 to day 7 by injection of the abdomen(ip),and were treated as groupⅢ.Ⅴ12g/kg AM after CDDP group: animals were received 12g/kg AM from the day 3 to day 7 by injection of the abdomen(ip),and were treated as groupⅢ.Rats were killed on the day 7. Nephrotoxicity was assessed by the measurements of body weight,kidney index, contents of serum creatinine,blood urea nitrogen and changes in histomorphology.Results After 6.0mg/kg CDDP ip administration,significant nephrotoxicity appeared in rats,including the significant decrease of body weight,increase of kidney index.The contents of serum creatinine and blood urea nitrogen were significantly higher than of the control(P＜0.05).Histologically,we observed impairment of brush border and microvillus,degeneration,necrosis of renal tubule cell,impairment of mitochondria and apoptosis.AM pretreatment would alleviate the above changes,which indicated the protective effect of AM on CDDP-induced nephrotoxicity.The protective effect of high doses AM before CDDP was much better than low doses AM before CDDP and high doses AM after CDDP.Conclusion 1.The way that rats were received 6mg/kg CDDP by injection of the abdomen to establish the cisplatin-induced kidney damage model is convenient,stable and good at reproducibility.2.It reveal that the administration of AM,to some exten,could prevent the nephrotoxicity induced by CDDP in rats.3.AM could obviously relieve the impairment of brush border and microvillus,mitochondria and inhibit apoptosis,it might be one of main mechanisms that AM could protect the rat kidney from beening injuried by CDDP.4.The protective effects of high dose AM on the cisplatin-induced kidney damage in rats is much better than low dose,The utilization of AM 2 days before CDDP is much better than the utilization of AM after CDDP.