Two Benzene Rings with a Boron Atom Comprise the Core Structure of 2-APB Responsible for the Anti-Oxidative and Protective Effect on the Ischemia/Reperfusion-Induced Rat Heart Injury.

To identify the core structure of 2-aminoethoxydiphenyl borate (2-APB) responsible for the anti-oxidative and protective effect on the ischemia/reperfusion (I/R)-induced heart injury, various 2-APB analogues were analyzed, and several antioxidant assays were performed. Cell viability was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Myocardial infarct size was quantified using triphenyl tetrazolium chloride (TTC) staining. The levels of tumor necrosis factor-alpha (TNF-α) and cleaved-caspase-3 protein were evaluated as an indicator for the anti-inflammatory and anti-apoptotic effect, respectively. Our data show that 2-APB, diphenylborinic anhydride (DPBA) and 3-(diphenylphosphino)-1-propylamine (DP3A) all exerted the anti-oxidative activity, but only 2-APB and DPBA can scavenge H2O2. 2-APB and DPBA can potently inhibit hydrogen peroxide (H2O2)- and hypoxanthine/xanthine oxidase (HX/XOD)-induced increases in intracellular H2O2 and H9c2 cell death. 2-APB and DPBA were able to decrease the I/R-induced adult rat cardiomyocytes death, myocardial infarct size, and the levels of malondialdehyde (MDA) and creatine kinase-MB (CK-MB). Our results suggest that the two benzene rings with a boron atom comprise the core structure of 2-APB responsible for the anti-oxidative effect mediated through the reaction with H2O2 and generation of phenolic compounds, which in turn reduced the I/R-induced oxidative stress and injury in the rat heart.

Methyl palmitate protects heart against ischemia/reperfusion-induced injury through G-protein coupled receptor 40-mediated activation of the PI3K/AKT pathway.

This study aimed to investigate whether methyl palmitate (MP) exerts cardioprotective effect against the ischemia/reperfusion (I/R) injury and its mechanisms underlying. The cultured adult cardiomyocytes were treated with vehicle or lactic acid ischemic buffer (pH 6.8) during hypoxia/reoxygenation. In addition, the cardioprotective effect of MP was evaluated using the ex vivo heart model of I/R injury. Here, we found that MP significantly reduced the I/R-induced cardiomyocyte death. Treatment with GW1100 (a GPR40-antagonist) or wortmannin (a phosphatidylinositol 3-kinase, PI3K, specific inhibitor) significantly attenuated the level of phospho-AKT (p-AKT) and abolished the MP-induced cardioprotection against the I/R-induced injury. Using the ex vivo I/R model, we also demonstrated that pretreatment with MP significantly reduced the size of myocardial infarction and the levels of cleaved-caspase 3 and MDA, and increased the protein levels of GPR40 and p-AKT induced by I/R. The cardioprotective effect of MP was evaluated also using the in vivo heart model of I/R injury. We demonstrated that post-ischemic treatment with MP significantly attenuated the size of myocardial infarction and the serum level of CK-MB induced by in vivo I/R model. Taken together, our data suggest that MP could provide significant cardioprotection against the I/R injury, and the underlying mechanisms by which MP prevented the cardiomyocyte death might be mediated through the GPR40-activated PI3K/AKT signaling pathways. These findings suggest the potential applications of MP in the treatment of I/R-induced heart injury.