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Sex Differences in the Oxidative Stress Level and Antioxidative Enzymes Activity in Obese Pre-Diabetic Elderly Rats Treated with Metformin or Liraglutide

Introduction: Diabetes mellitus and obesity increase the level of oxidative stress. This study aimed to determine serum level of oxidative stress and antioxidative enzymes activity in pre-diabetic obese elderly Sprague- Dawley (SD) rats of both sexes, treated with metformin (increases insulin sensitivity) or liraglutide (glucagon-like peptide-1 receptor agonist who stimulates insulin secretion). Methods: Male and female SD rats were divided in:1)control group ; 2)group fed high fat-high salt diet (HSHFD) from 20-65 weeks of age ; 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, after which rats were sacrificed for serum collection and measurement of Ferric reducing ability of plasma (FRAP), Thiobarbituric Acid Reactive Substances (TBARS) and SOD, catalase and gluthatione peroxidaseactivity by spectrophotometry. Results: No difference in TBARS among female rat groups was observed. FRAP was significantly higher in HFHSD+Liraglutid compared to HFHSD+Metformin and HSHFD groups. Catalase activity was higher in control group compared to other female groups. TBARS and FRAP were similar among male groups. Control males 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 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 group of rats.Treatment with liraglutide increased FRAP compared to HFHSD+metformin and HFHSD groups in female to control levels, but TBARS 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. Presence of metformin and liraglutide decrease activity of antioxidative enzymes in male. Sources of Funding: This work has been supported in part by VIF-MEFOS-15 (Faculty of Medicine Osijek, Croatia) and by RECOOP HST grant. Ethical Approval: Hungarian Ethical Committee for Animal Research (IV/3796/2015). Acknowledgement: The study was supported by Cedars Sinai Medical Center’s International Research and Innovation in Medicine Program, the Association for Regional Cooperation in the Fields of Health, Science and Technology (RECOOP HST Association) and the participating Cedars – Sinai Medical Center - RECOOP Research Centers (CRRC).

antioxidative enzymes activity; TBARS; FRAP; diabetes; obesity

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