Effect of SGLT2 Inhibitor on Cardiomyopathy in a Rat Model of T2DM: Possible involvement of Cardiac Aquaporins.

ABSTRACT

Diabetic cardiomyopathy (DCM) causes arrhythmia, heart failure, and sudden death. Empagliflozin, an SGLT-2 (Sodium glucose co-transporter) inhibitor, is an anti-diabetic medication that decreases blood glucose levels by stimulating urinary glucose excretion. Several aquaporins (AQPs) including AQP-1-3 and - 4 and their involvement in the pathogenesis in different cardiac diseases were detected. In the current study the effect of Empagliflozin on diabetic cardiomyopathy and the possible involvement of cardiac AQPs were investigated. METHODS: 56 adult male Sprague-Dawley rats were divided into 4 groups Control, DCM type 2 diabetic rats, low EMPA+DCM received empagliflozin (10 mg/kg/day) and high EMPA+DCM received empagliflozin (30 mg/kg/day) for 6 weeks. RESULTS: Administration of both EMPA doses, especially in high dose group, led to significant improvement in ECG parameters. Also, a significant improvement in biochemical and cardiac oxidative stress markers (significant decrease in serum CK-MB, and malondialdehyde while increasing catalase) with decreased fibrosis and edema in histopathological examination and a significant attenuation in apoptosis (caspase-3) and edema (AQP-1& -4). CONCLUSION: Both doses of Empagliflozin have a cardioprotective effect and reduced myocardial tissue edema with high dose having a greater effect. This might be due to attenuation of oxidative stress, fibrosis and edema mediated through AQP-1, - 3& - 4 expression.