Sex differences in oxidative stress level and antioxidative enzymes expression and activity in obese pre-diabetic elderly rats treated with metformin or liraglutide

二甲双胍或利拉鲁肽治疗肥胖糖尿病前期老年大鼠氧化应激水平及抗氧化酶表达与活性的性别差异

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作者:Anita Matić, Rosemary Vuković, Marija Heffer, Marta Balog, Vedrana Ivić, Robert Gaspar, Eszter Ducza, Kalman F Szucs, Adrienn Seres, Sandor G Vari, Ines Drenjančević

Aim

To determine the effects of metformin or liraglutide on oxidative stress level and antioxidative enzymes gene expression and activity in the blood and vessels of pre-diabetic obese elderly Sprague-Dawley (SD) rats of both sexes.

Conclusions

Obesity and antidiabetic drugs caused sex-related differences in the level of antioxidative parameters. Liraglutide exhibited stronger antioxidative effects than metformin. These results indicate that weight gain due to HSHFD is crucial for developing oxidative stress and for inhibiting antioxidative protective mechanisms.

Methods

Male and female SD rats were assigned to the following groups: a) control group (fed with standard rodent chow); b) high-fat and high-carbohydrate diet (HSHFD) group fed with HSHFD from 20-65 weeks of age; c) HSHFD+metformin treatment (50 mg/kg/d s.c.); and d) HSHFD+liraglutide treatment (0.3 mg/kg/d s.c). Oxidative stress parameters (ferric reducing ability of plasma and thiobarbituric acid reactive substances) and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activity and gene expression were determined from serum, aortas, and surface brain blood vessels (BBV).

Results

HSHFD increased body weight in both sexes compared with the control group, while liraglutide prevented this increase. Blood glucose level did not change. The liraglutide group had a significantly increased antioxidative capacity compared with the HSHFD group in both sexes. The changes in antioxidative enzymes' activities in plasma were more pronounced in male groups. The changes in antioxidative gene expression were more prominent in microvessels and may be attributed to weight gain prevention. Conclusions: Obesity and antidiabetic drugs caused sex-related differences in the level of antioxidative parameters. Liraglutide exhibited stronger antioxidative effects than metformin. These results indicate that weight gain due to HSHFD is crucial for developing oxidative stress and for inhibiting antioxidative protective mechanisms.

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