Dichloroacetate ameliorates myocardial ischemia-reperfusion injury via regulating autophagy and glucose homeostasis

INTRODUCTION: Autophagy occurs in response to myocardial ischemia-reperfusion (I/R) injury and plays both a protective and detrimental role in this pathological process. Dichloroacetate (DCA) has a protective role during myocardial I/R injury, but its effects on autophagy induction are less well understood. We established a rat myocardial I/R injury model and investigated the effects of DCA on autophagy induction. MATERIAL AND METHODS: Healthy Sprague-Dawley (SD) rats were used to establish a myocardial I/R model. The effect of DCA on cardiac infarct size, cardiac function, and serum levels of serum creatine kinase (CK), lactic dehydrogenase (LDH) and cardiac troponin I (cTnI) during I/R injury were assessed. Using cultured rat cardiac myocytes, we investigated the functional implications of DCA and explored the relevant mechanism(s) of DCA protection during I/R injury. RESULTS: DCA significantly decreases infarct size and arrhythmia scores, increases heart rate (HR), left ventricular developed pressure (LVDP), the maximal rate of pressure rise (+dp/dtmax) and coronary flow (CF), and reduces the levels of CK, LDH and cTnI after I/R. DCA treatment enhanced myocardial cell viability and alleviated apoptosis assessed through TUNEL assays and Bcl-2/Bax expression. Notably, the levels of the autophagy biomarkers Beclin-1, LC3II and reactive oxygen species (ROS) significantly decreased following DCA treatment. When Bcl-2 was silenced, Beclin-1 expression significantly decreased following DCA treatment, suggesting that DCA confers a protective role during I/R injury through autophagy regulation. Moreover, DCA was found to regulate glucose homeostasis through increasing the expression of Glut-1 and Glut-4. CONCLUSIONS: DCA contributes to I/R injury protection through the regulation of autophagy and glucose homeostasis.