Dysregulation of hepatic superoxide dismutase, catalase and glutathione peroxidase in diabetes: response to insulin and antioxidant therapies.
Recent evidence suggests that impaired antioxidant status is involved in oxidative stress associated with diabetes. The main antioxidant enzymes include superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX). The aim of the present investigation was to evaluate the activities and protein expression of these antioxidant enzymes in streptozotocin-induced diabetes. Furthermore, the effects of insulin and antioxidant therapy alone and in combination were studied. Male Sprague-Dawley rats were rendered diabetic by streptozotocin administration and randomly assigned to untreated, insulin-treated, antioxidant (vitamin E and C)-treated and insulin plus antioxidant-treated groups. Normal rats fed either a regular diet or the antioxidant (vitamin E and C)-rich diet served as controls. The animals were observed for 4 weeks. Diabetic animals showed marked weight loss, decreased activities of Cu Zn SOD and CAT and normal GPX activity. Additionally, the expression of all antioxidant enzyme proteins was decreased in the diabetic rats compared to the untreated controls. Insulin therapy prevented weight loss and normalized the activities and protein expression of all antioxidant enzymes. Antioxidant therapy in the diabetic rats normalized Cu Zn SOD and GPX protein expression. Combined therapy with insulin and antioxidants normalized all measured antioxidant enzyme protein expression and activities. Thus diabetes-associated reductions in antioxidant enzymes can be ameliorated by insulin and/or antioxidant therapy.
Division of Nephrology and Hypertension, Department of Medicine, University of California, Irvine, California 92697-4066, USA. rksindhu@uci.edu
Ram K
RK
Sindhu
Ja-Ryung
JR
Koo
Christian K
CK
Roberts
Nosratola D
ND
Vaziri
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D002374:Catalase / Q000187:drug effects / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000201:enzymology*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005979:Glutathione Peroxidase / Q000187:drug effects / Q000378:metabolism*; D006943:Hyperglycemia / Q000188:drug therapy / Q000201:enzymology; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000627:therapeutic use; D008099:Liver / Q000201:enzymology*; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008955:Models, Cardiovascular; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000187:drug effects / Q000378:metabolism*; D016896:Treatment Outcome
D000975:Antioxidants; D015415:Biomarkers; D007004:Hypoglycemic Agents; D007328:Insulin; D008315:Malondialdehyde; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase