Empagliflozinin Sıçanlarda Doksorubisin ile Oluşturulan Kardiyomiyopati Üzerine Etkisi

Abstract

Barış V.Ö. Empagliflozin’s Effect on Doxorubicin induced Cardiyomyopathy in Rats Hacettepe University Graduate School of Health Sciences, Doctor of Philosophy Thesis for Physiology, Ankara, 2021 Empagliflozin is an SGLT-2 inhibitor that reduces cardiovascular deaths and hospitalizations for heart failure. In this study, we aimed to evaluate the possible protective effects of empagliflozin against doxorubicin-induced cardiotoxicity. Non-diabetic Sprague-Dawley rats were randomly divided into four groups in this study. Physiological saline (SF) (1 ml) was given to the control group by intraperitoneal (I.P.) and orogastric (O.G.) routes, and to the EMPA group empagliflozin 10 mg/kg/day by O.G. route, SF was given by I.P. route. DOX group as a cumulative 18 mg / kg body weight / 6 days doxorubicin by IP route, SF was given via O.G. route. Doxorubicin and empagliflozin were administered at the same doses for 14 days to the DOX + EMPA group. On the 15th day, echocardiographic and electrocardiographic examinations were performed under anesthesia. Blood samples were taken to evaluate biochemical parameters and heart tissues were excised to evaluate histopathological findings. Left ventricular systolic (P <0.05) and diastolic diameters (P <0.01), QTc interval (P <0.001), karyololysis and karyorexis ratio (P <0.001) and infiltrative cell proliferation (P < 0.01) in the DOX group compared to the control group 0.001), while left ventricular ejection fraction, fractional shortening and normal cell morphology were found to be lower (P <0.001). In the DOX + EMPA group; Compared to the Dox group, left ventricular diastolic diameters (P <0.05) and systolic (P <0.01) diameters, QTc interval (P <0.001), karyolysis and karyorexis rates (P <0.001) and infiltrative cell proliferation were significantly lower. (P < 0.01); normal cell morphology and left ventricular ejection fraction were significantly higher than in the DOX group (P <0.001). Biochemical results were similar between groups. As a result; This study showed that empagliflozin significantly improved doxorubicin-induced QTc prolongation, left ventricular dilatation, left ventricular systolic dysfunction, infiltrative cell proliferation and necrosis. The data obtained in the current study indicate that the protective effect of empagliflozin is due to the increase in mitochondrial biogenesis and prevention of sarcoplasmic reticulum degeneration rather than natriuretic or antioxidant effects.