2137-PUB: Exercise and Stevia R. Extracts Attenuate Diabetic Cardiomyopathy in Type 2 Diabetic Rats via Upregulation of Nrf2 and Suppression of Oxidative Stress, Fibrosis, Apoptosis, and Sympathetic Overactivity

Abstract

Objectives: In the current work, we studied the effects of exercise and stevia extracts on diabetic cardiomyopathy in type 2 diabetic rats and their possible underlying mechanisms.

Methods: Thirty-two male Sprague Dawley rats were randomly allocated into 4 equal groups; a) normal control group, b) DM group, type 2 diabetic rats received 2ml oral saline daily for 4 weeks, c) DM+ Exercise, type 2 diabetic rats were treated with exercise for 4 weeks and d) DM+ stevia extracts: type 2 diabetic rats received methanolic stevia extracts. By the end of experiment, serum blood glucose, HOMA-IR, insulin and cardiac enzymes (LDH, CK-MB), cardiac histopathology, oxidative stress markers (MDA, GSH and CAT), myocardial fibrosis by Masson trichrome, the expression of p53, α-SMA and tyrosine hydroxylase (TH) by immunostaining in myocardial tissues were measured. Also, the expression of nuclear factor erythroid-like factor 2 (nrf2) was measured in myocardial tissues.

Results: We found that T2DM caused significant increase in blood glucose, HOMA-IR index, serum CK-MB and LDH, myocardial damage and fibrosis, myocardial MDA, myocardial α-SMA, p53, nrf2 and TH density with significant decrease in serum insulin and myocardial GSH and CAT. On the other hand, treatment with either exercise or stevia extracts caused in significant improvement in studied parameters.

Conclusions: exercise and methanolic stevia extracts have cardioprotective effects against DCM, which might be due to attenuation of fibrosis, oxidative stress, p53, TH and upregulation of nrf2. Moreover, stevia extracts offered more protective effect than exercise.