Resveratrol Prevents Diabetic Cardiomyopathy by Increasing Nrf2 Expression and Transcriptional Activity

الملخص EN

Objective.

This study investigated if resveratrol ameliorates diabetic cardiomyopathy by targeting associated oxidative stress mechanisms.

Method.

Type 1 diabetes mellitus (DM) in FVB mice was induced by several intraperitoneal injections of a low dose of streptozotocin.

Hyperglycemic and age-matched control mice were given resveratrol (10 mg/kg per day) for 1 month and subsequently monitored for an additional 6 months.

Mice were assigned to four groups: control, resveratrol, DM, and DM/resveratrol.

Cardiac function and blood pressure were assessed at 1, 3, and 6 months after DM induction.

Oxidative damage and cardiac fibrosis were analyzed by histopathology, real-time PCR, and Western blot.

Result.

Mice in the DM group exhibited increased blood glucose levels, cardiac dysfunction, and high blood pressure at 1, 3, and 6 months after DM induction.

Resveratrol did not significantly affect blood glucose levels and blood pressure; however, resveratrol attenuated cardiac dysfunction and hypertrophy in DM mice.

Resveratrol also reduced DM-induced fibrosis.

In addition, DM mice hearts exhibited increased oxidative damage, as evidenced by elevated accumulation of 3-nitrotyrosine and 4-hydroxynonenal, which were both attenuated by resveratrol.

Mechanistically, resveratrol increased NFE2-related factor 2 (Nrf2) expression and transcriptional activity, as well as Nrf2’s downstream antioxidative targets.

Conclusion.

We demonstrated that resveratrol prevents DM-induced cardiomyopathy, in part, by increasing Nrf2 expression and transcriptional activity.