Effects of probucol on oxidative stress in rats with diabetic nephropathy

Abstract

Objective To investigate the antioxidant effects of probucol(PB) on oxidative stress in diabetic nephropathy(DN) rats.Methods 60 Sprague-Dawley(SD) male rats were randomly divided into four groups:normal control group(NC group,n =8),right renal blood vessel ligation group (RL group,n =8),DN group(n =22),DN + PB group (n =22).The right renal blood vessels were ligated in RL group,DN group and DN + PB group.After a week the diabetic model was established by intravenous injection of alloxan with the dose of 50 mg/kg in DN group and DN + PB group.82.5％ of rats whose 72 h blood glucose level were higher than 16.7 mmol/L were considered to be valid diabetic models.The rats in DN + PB group were administrated with PB 170 mg/(kg · d) by a gastric tube for 3 weeks.The rats survived to the end of the experiment were 8 in NC group,6 in RL group,5 in DN group,8 in DN +PB group.24 h urine was collected before the rats were sacrificed.24 h urinary microalbumin (UMA),the kidney hypertrophy index (LK/BW),blood glucose (BG),blood urea nitrogen (BUN),creatinine (Cr),total cholesterol (TC),triglyceride (TG),low density lipoprotein (LDL),very low density lipoprotein (VLDL),high density lipoprotein (HDL) were respectively examined.The activities of malondialdehyde (MDA),superoxide dismutase (SOD),catalase (CAT) and glutathione peroxidase (GSH-PX) were measured.The left kidney was stained by HE for pathological examination.Results Compared with those in NC group and RL group,BG and LK/BW were significantly increased in rats of DN group and DN + PB group (P ＜ 0.05).The levels of BUN,Cr,24 h UMA,LDL,MDA were significantly increased (P ＜ 0.05) and the levels of SOD,CAT,SOD/MDA were significantly decreased(P ＜ 0.05) in rats of DN group,compared with those in NC group,RL group and DN + PB group.And the parameters mentioned above were significantly improved in rats of DN + PB group,compared with those in DN group(P ＜0.05).The level of GSH-PX increased in RL group,DN group and DN + PB group,compared with NC group(P ＜ 0.05),but it had no significant difference in RL group,DN group and DN + PB group (P ＞ 0.05).The levels of TC,TG,HDL and VLDL had no statistical difference among the four groups (P ＞ 0.05).BG,BUN,Cr,24 h UMA,LK/BW,LDL had positive correlations with MDA (P ＜ 0.01) and had negative correlations with SOD and SOD/MDA (P ＜ 0.01).The size of glomerular volume,the thickeness of glomerular basement membrane and arterial wall,the hyperplasia of glomerular mesangial matrix on renal tissue pathology had improved in DN + PB group,compared with DN group.Conclusion MDA and MDA/SOD may act as two sensitive markers to valuate oxidative and antioxidative state.PB may improve the activity of antioxidative enzyme in DN rats,reduce the concentration of oxidative substance,and provide a renoprotective effect.Antioxidative treatment could be a potential therapeutic procedure for DN. Key words: Diabetic nephropathy ;  Alloxan ;  Probucol;  Oxidative stress