engleski

Different antioxidative enzymes expression in aorta and brain blood vessels in obese prediabetic elderly rats of both sexes treated with metformin or liraglutide

Introduction: This study aimed to determine differences in micro and macrovascular antioxidative enzymes gene expression of pre-diabetic obese elderly Sprague-Dawley (SD) rats of both sexes. Additionally, study aimed to determine whether liraglutide and meformin change the gene expression of antioxidative enzymes in this model. Methods: Male and female SD rats were divided in: CONTROL group (fed with standard rat food) ; HSHFD group fed with commercially available carbohydrate and fat rich food from 20- 65 weeks of age ; HSHFD+metformin treatment (50 mg/kg/day s.c.) and HSHFD+liraglutide treatment (0.3 mg/kg/day s.c). During the entire protocol rats have free access to food and tap water. Animals were anesthetized with isoflurane (Forane® isofluranum). Aortas and brain blood vessels (BBV) were used to determine superoxide dismutase (SOD) izoforms, glutathione peroxidases 1 and 4 (GPx1 and GPx4) and catalase (CAT) gene expression. Results: No significant enzymes expression differences were observed among male aortas, while in female HSHFD+liraglutide aortas, expression of Cu/Zn SOD, EC-SOD, GPx1 and CAT was increased compared to other studied group. MnSOD, EC-SOD and GPx1 gene expression in female CONTROL BBV group was significantly increased compared to other female groups and EC-SOD and GPx4 in male CONTROL BBV was significantly increased compared to other studied male groups. Discussion: There are sex and vascular site differences in gene expression of different antioxidative enzymes and resulting changes are more evident in macrovessels. Drugs may modify oxidative status more in female than male. Conclusions: Obesity significantly reduces the expression of antioxidant enzymes particularly in macrovasculature of both sexes. Our results showed that more significant changes are observed in the expression of antioxidative enzymes in macrovessels (aortas) than in the microcirculation (BBV) in female and male with/without application of drugs. The liraglutide therapy proved to be more effective in reducing oxidative stress than metformin by increasing expression of antioxidative enzymes more strongly, especially in females.

obesity, oxidative stress, blood vessels, antioxidative enzymes, liraglutide, metformin

Ethical Approval All experimental procedures are conformed to the European Guidelines for the Care and Use of Laboratory Animals (Directive 86/609). They were approved by Hungarian Ethical Committee for Animal Research (IV/3796/2015). Sources of Funding The study was supported in part by Bohdan Malaniak CSMC - RECOOP Young Scientists Research and by VIF-MEFOS-15 (Faculty of Medicine Osijek, Croatia). Acknowledgements 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 Cedars – Sinai Medical Center - RECOOP Research Centers (CRRC) and VIF-MEFOS-15 (Faculty of Medicine Osijek, Croatia).