Probucol Prevents Cisplatin-induced Nephrotoxicity In Rat

Objectives:To evaluate the relationship among oxidative stress, nuclear transcription factor Sp1 and cell apoptosis in kidney damage rats induced by cisplatin;Probucol was administered to confirm its protective role against nephrotoxicity induced by cisplatin.Methods:Twenty four male adult Sprague-Dawley rats were randomly divided into four groups(6 rats in each group),namely normol control(CN),cisplatin(CP),cisplatin+probucol(CP+ probucol),probucol control(probucol).Excpect CP+ probucol and probucol groups received 1%probucol diet,other groups received normal diet until the end of trial. In 14th day of experiment,CN and probucol groups were injected intraperitoneally(i.p.) with saline 1ml/200g,CP and CP+ probucol groups received single dose of cisplatin 6mg/kg i.p..Collection the 24 h urine of rats before injection cisplatin 24 h and 24h after injection, measurement of urinary N-Acetyl-β-D- glucosaminidase(NAG),after injection cisplatin 48 h,use 10%chloral hydrate anesthesia rats,then pick eye to collection blood measurement of serum creatinine(Scr) and blood urea nitrogen(BUN),The extent of lipid peroxidation in the kidney was evaluated by measuring malondialdehyde(MDA) and glutathione peroxide(GSH-Px) in the kidney tissue homogenate.The renal injury was also assessed by hematoxylin and eosin and TdT-mediated deoxyuridine nick end-labelling staining.Expression of Sp1 protein in renal tissue was detected by immunohistochemical staining.Records:Cisplatin caused an increase kidney index,BUN and serum creatinine levels,urinary NAG,MDA in the kidney tissue(P＜0.01); decreased the renal GSH-Px activity;significant increase of Tubular injury and renal tubular cell apoptosis.(P＜0.01);the expression of Sp1 was increased.Probucol caused an decrease kidney index,BUN and serum creatinine levels,urinary NAG,MDA in the kidney tissue(P＜0.05, P＜0.01,P＜0.05,P＜0.05);increased the renal GSH-Px activity;significant decrease of Tubular injury and renal tubular cell apoptosis.(P＜0.01);the expression of Sp1 was decreased.Conclusions:Oxidative stress and Sp1 play an important role in cisplatin-induced nephrotoxicity in rats.Probucol protected the renal tissue from nephrotoxicity induced by cisptatin,the protective mechanism may be partly through anti-oxidation,inhibition of cell apoptosis,reduced the expression of Sp1 protein in the renal tissue.