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

Abstract

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.

Crucial Role of Stromal Interaction Molecule-Activated TRPC-ORAI Channels in Vascular Remodeling and Pulmonary Hypertension Induced by Intermittent Hypoxia

“…These results suggest that the effects of antioxidants may be related with the inactivation of STOC and subsequently decrease in intracellular calcium. Although an antioxidant action of 2-APB has been shown in ischemia/reperfusion damage in mice and rat cardiomyocytes ( Morihara et al, 2017 ; Shen et al, 2021 ), our results showed that 2-APB did not prevent the systemic and lung oxidative stress, suggesting that the effects of 2-APB on PASMC in the lung are not related by a reduction in oxidative stress. Thus, it is likely that the effects of 2-APB were related to its inhibitory action on the increased intracellular Ca 2+ concentrations induced by STOC ( Bootman et al, 2002 ).…”

“…Accordingly, to assess the contribution of STOC on the CIH-induced pulmonary vascular alterations, we study the effects of the STOC non-selective inhibitor 2-aminoethyldiphenylborinate (2-APB) ( Bootman et al, 2002 ; Smith et al, 2015 ; Castillo-Galán et al, 2016 , 2022 ; Jain et al, 2021 ) on the development of pulmonary hypertension and vascular remodeling induced by CIH in a well stablished preclinical model of OSA ( Del Rio et al, 2010 , 2012 , 2014 ; Iturriaga et al, 2014 , Iturriaga and Castillo-Galán, 2019 ). We also determined the effects of 2-APB on systemic and lung oxidative stress induced by CIH, because 2-APB ameliorates the oxidative stress in a heart ischemia-reperfusion model in mice ( Morihara et al, 2017 ) and rat ( Shen et al, 2021 ).…”

RIP3 Contributes to Cardiac Hypertrophy by Influencing MLKL-Mediated Calcium Influx

“…Interestingly, Brundel et al found that LaCl 3 treatment prevents structural changes in a pacing-induced cellular remodeling in a HL-1 myocyte model for atrial fibrillation [ 43 ]. In 2021, Shen et al reported that 2-APB treatment decreases the I / R -induced adult rat cardiomyocytes death and myocardial infarct size [ 44 ]. These findings suggest that LaCl 3 and (or) 2-APB may possess beneficial effects on cardiovascular diseases.…”