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Markers of blood oxidative stress and antioxidative enzymes activity in obese diabetic elderly rats treated with Metformin or Liraglutide

Introduction: Diabetes mellitus and obesity present with increased oxidative stress. Metformin increases insulin sensitivity and influences glucose metabolism in liver and in peripheral tissues. Liraglutide is a glucagon- like peptide-1 receptor agonistthat stimulates insulin secretion.This study aimed to determine the markers of oxidative stress in diabetic obese elderly Sprague-Dawley (SD) rats treated with metformin or liraglutide. Methods: Male and female SD rats were divided in: 1) control group ; 2) group fed high fat- high salt diet from 20 to 65 weeks of age (HSHFD) ; 3) HSHFD+Metformin (50 mg/kg/day s.c.) ; and 4) HSHFD+Liraglutide (0.3 mg/kg/day s.c). Drugs were given concomitantly to HSHFD from 51-65 weeks of age when rats were sacrificed. Plasma lipid peroxidation products were assessed by TBARS andantioxidative capacity by FRAP. SOD, catalase and gluthatione peroxidase activity was assessed by spectrophotometry. Results: Female: no difference in TBARS among groups. FRAP was significantly higher in HFHSD+Liraglutid compared to HFHSD+Metformin and HSHFD.Catalase activity was higher in control compared to other female groups. Male: TBARS and FRAP were similar among male groups. Control group had higher catalase activity compared to other male groups ; higher GPx activity compared to HSHFD+metformin and HSHFD+liraglutide and higher SOD activity compared to HSHFD+metformin. Female vs. male: Female control rats had significantly higher TBARS compared to male control. Catalase activity was significantly decreased in all diet groups of both sexes compared to respective control groups and decreased in female groups overall, compared to male. Discussion: Metformin significantly decreased all antioxidative enzymes activity compared to control in male.Treatment with liraglutide increased antioxidant capacity compared to HFHSD+metformin and HFHSD groups in female to control levels, but oxidative stress was not significantly changed. Conclusion: There are sex-related differences in the level of oxidative stress and antioxidative enzymes activity. Drugs may modify antioxidative capacity more in female than male. Metformin and liraglutide decrease activity of antioxidative enzymes in male.

antioxidative enzymes activity; TBARS; FRAP; diabetes; obesity

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