Bezafibrate mitigates cardiac injury against coronary microembolization by preventing activation of p38 MAPK/NF-κB signaling.

Abstract

Coronary microembolization (CME)-induced inflammatory response and cardiomyocyte apoptosis are the main contributors to CME-associated myocardial dysfunction. Bezafibrate, a peroxisome proliferator-activated receptors (PPARs) agonist, has displayed various benefits in different types of diseases. However, it is unknown whether Bezafibrate possesses a protective effect in myocardial dysfunction against CME. In this study, we aimed to investigate the pharmacological function of Bezafibrate in CME-induced insults in myocardial injury and progressive cardiac dysfunction and explore the underlying mechanism. A CME model was established in rats, and cardiac function was detected. The levels of injury biomarkers in serum including CK-MB, AST, and LDH were determined using commercial kits, and pro-inflammatory mediators including TNF-α and IL-6 were detected using ELISA kits. Our results indicate that Bezafibrate improved cardiac function after CME induction. Bezafibrate reduced the release of myocardial injury indicators such as CK-MB, AST, and LDH in CME rats. We also found that Bezafibrate ameliorated oxidative stress by increasing the levels of the antioxidant GPx and the activity of SOD and reducing the levels of TBARS and the activity of NOX. Bezafibrate inhibited the expression of pro-inflammatory cytokines such as TNF-α and IL-6. Importantly, Bezafibrate was found to mitigate CME-induced myocardial apoptosis by increasing the expression of Bcl-2 and reducing the levels of Bax and cleaved caspase-3. Mechanistically, Bezafibrate could prevent the activation of p38 MAPK/NF-κB signaling. These findings suggest that Bezafibrate may be a candidate therapeutic agent for cardioprotection against CME in clinical applications.