The Role of Mitochondrial ATP-Sensitive Potassium Channels in Cardioprotective and Anti-Inflammatory Effects of Troxerutin in Myocardial Reperfusion Injury

A major clinical challenge in ischemic heart disease is the prevention of myocardial injury following ischemia/reperfusion (i/r). application of natural pharmaceuticals seems to be clinically interesting due to their multiplex activities. protective effects of troxerutin (txr) in myocardial i/r injury have been ever demonstrated, nevertheless, the purpose of this study is to explore the role of mitochondrial adenosine triphosphate -sensitive potassium (mitokatp) channels and toll-like receptor 4 (tlr4)-nuclear factor kappa b (nf-κb) pathway in cardioprotective effects of txr against i/r injury in rats. male wistar rats (n=72, 250–300 g, 12 weeks old) were randomized into groups with/without i/r and/or txr and 5-hydroxydecanoate (5-hd), alone or in combination. to induce i/r model, the langendorff-perfused hearts were subjected to left anterior descending coronary artery (lad) ligation and re-opening. txr (150mg/kg/day) was administered for 4 weeks before i/r. moreover, 5-hd (100 μm) was added to the perfusion solution before the ischemia. finally, myocardial infarct size, ldh release, protein expression levels of tlr4 and nf-κb, and the levels of pro-inflammatory cytokines (tnf-α and il-1β) were assessed. txr preconditioning significantly reduced is and ldh release (p<0.05). furthermore, it decreased the expression of tlr4 and nf-κb and the level of pro-inflammatory cytokines (p<0.05 to p<0.01). inhibition of mitokatp channels by 5-hd significantly reversed the cardioprotective effects of txr. this work shed some light on the knowledge about the mechanisms involved in the anti-inflammatory effect of txr preconditioning in myocardial i/r injury. this effect may be partly mediated through mitokatp channels opening and subsequent suppression of the tlr4/nf-κb pathway.