Effects of simvastatin on oxidative stress in streptozotocin-induced diabetic rats: a role for glomeruli protection.
OBJECTIVE
To study the effects of simvastatin on oxidative stress in rats with early stage diabetic nephropathy.


METHODS
60 male Sprague-Dawley rats were divided into three groups: control group (CN), streptozotocin (STZ)-induced diabetic rats group (DM) and STZ-induced diabetic rats group treated with simvastatin (DM+S). The following parameters were measured at weeks 6 and 12 in similar rats chosen randomly from each group: body and kidney weight, 24-hour urinary albumin excretion (UAE), biochemical indexes including blood glucose (GLU), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TG), serum creatinine (SCr), antioxidant enzymes including superoxide dismutase (SOD), glutathione S-transferase (GST), catalase (CAT) in plasma, lipid peroxidation production as malondialdehyde in plasma (MDAp) and erythrocytes (MDAe), morphology parameters such as glomerular volume (GV) and mesangial area/total glomerular area (M/T).


RESULTS
At weeks 6 and 12, GLU and kidney weight to body weight ratio were notably increased in both of the diabetic groups compared with those in the CN group without significant differences between the two diabetic groups. There were no significant differences of SCr, LDL, HDL and TG among all groups within all the experimental time. MDAp and MDAe were significantly increased in both of the diabetic groups, especially at week 12, while SOD, GST and CAT were significantly decreased compared with those in the CN group. At week 12, GV, M/T and UAE were also increased in the two diabetic groups. However, in the DM+S group, changes of lipid peroxidation production, antioxidant enzymes, UAE and GV were less pronounced than those in the DM group. Pearson's correlation analysis and regression analysis shown that MDAp was increased while SOD, GST and CAT in plasma were decreased with elevation of UAE, GV and M/T.


CONCLUSIONS
Increased lipid peroxidation and decreased antioxidant enzymes in plasma may play a role in the progression of diabetic nephropathy. Simvastatin may ameliorate these changes to protect kidney from oxidative lesion in diabetes even in the absence of lipid abnormalities.
Zhu
Bin
B
Department of Nephrology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. zhubing@hotmail.com
Shen
Hanchao
H
Zhou
Junfu
J
Lin
Feili
F
Hu
Ying
Y
D000419:Albuminuria; D000818:Animals; D000975:Antioxidants; D001786:Blood Glucose; D002374:Catalase / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000503:physiopathology / Q000517:prevention & control*; D005982:Glutathione Transferase / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D007678:Kidney Glomerulus / Q000033:anatomy & histology / Q000473:pathology / Q000502:physiology*; D015227:Lipid Peroxidation; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D011507:Proteinuria; D051381:Rats; D017207:Rats, Sprague-Dawley; D019821:Simvastatin / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism; D014280:Triglycerides / Q000032:analysis
D000975:Antioxidants; D001786:Blood Glucose; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D000960:Hypolipidemic Agents; D014280:Triglycerides; D019821:Simvastatin; D002374:Catalase; D013482:Superoxide Dismutase; D005982:Glutathione Transferase