Troxerutin Preconditioning Modulates the Activity of TLR4/NF-κB Signaling Pathway and Mitochondrial ATP-Sensitive Potassium Channels in a Rat Model of Myocardial Ischemia/Reperfusion Injury

Abstract Purpose Given the rising prevalence of ischemic heart diseases (IHD), investigations for achieving effective treatments are required. The purpose of this study is further understanding of troxerutin's impact on inflammatory response induced by myocardial ischemia/reperfusion (MI/R) injury, and the role of toll-like receptor 4 (TLR4)-nuclear factor kappa B (NF-κB) signaling pathway and mitochondrial ATP-sensitive potassium (mitoKATP) channels in this scenario. Methods Sixty male Wistar rats were randomly divided into six groups: Control, troxerutin-receiving, MI/R, MI/R plus troxerutin, MI/R plus 5-hydroxydecanoate (5-HD), and MI/R plus troxerutin and 5-HD. The Langendorff-perfused hearts of animals were subjected to 30 min of left anterior descending coronary artery (LAD) ligation and 45 min of reperfusion. Troxerutin (150 mg/kg/day) was administered for 4 weeks prior to MI/R. 5-HD (100 µM) was added to the perfusion solution 20 min before the ischemia. Myocardial infarct size (IS), lactate dehydrogenase (LDH) release, the expressions of TLR4 and NF-κB, and the levels of tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) were measured. Results Troxerutin preconditioning significantly reduced IS (P < 0.05) and LDH release (P < 0.05). Pretreatment with troxerutin decreased the expressions of TLR4 (P < 0.05) and NF-κB (P < 0.01), and reduced the levels of TNF-α (P < 0.01) and IL-1β (P < 0.05). Inhibition of mitoKATP channels by 5-HD significantly reversed the cardioprotective effects of troxerutin (P < 0.05). Conclusion The present work revealed that troxerutin preconditioning has cardioprotective effects against MI/R damage, which are partly mediated through anti-inflammatory effects and the activation of mitoKATP channels.