2-aminoethoxydiphenyl borate provides an anti-oxidative effect and mediates cardioprotection during ischemia reperfusion in mice.

Author(s) Morihara, H.; Obana, M.; Tanaka, S.; Kawakatsu, I.; Tsuchiyama, D.; Mori, S.; Suizu, H.; Ishida, A.; Kimura, R.; Tsuchimochi, I.; Maeda, M.; Yoshimitsu, T.; Fujio, Y.; Nakayama, H.
Journal PLoS One
Date Published 2017
Abstract

Excessive levels of reactive oxygen species (ROS) and impaired Ca2+ homeostasis play central roles in the development of multiple cardiac pathologies, including cell death during ischemia-reperfusion (I/R) injury. In several organs, treatment with 2-aminoethoxydiphenyl borate (2-APB) was shown to have protective effects, generally believed to be due to Ca2+ channel inhibition. However, the mechanism of 2-APB-induced cardioprotection has not been fully investigated. Herein we investigated the protective effects of 2-APB treatment against cardiac pathogenesis and deciphered the underlying mechanisms. In neonatal rat cardiomyocytes, treatment with 2-APB was shown to prevent hydrogen peroxide (H2O2) -induced cell death by inhibiting the increase in intracellular Ca2+ levels. However, no 2-APB-sensitive channel blocker inhibited H2O2-induced cell death and a direct reaction between 2-APB and H2O2 was detected by 1H-NMR, suggesting that 2-APB chemically scavenges extracellular ROS and provides cytoprotection. In a mouse I/R model, treatment with 2-APB led to a considerable reduction in the infarct size after I/R, which was accompanied by the reduction in ROS levels and neutrophil infiltration, indicating that the anti-oxidative properties of 2-APB plays an important role in the prevention of I/R injury in vivo as well. Taken together, present results indicate that 2-APB treatment induces cardioprotection and prevents ROS-induced cardiomyocyte death, at least partially, by the direct scavenging of extracellular ROS. Therefore, administration of 2-APB may represent a promising therapeutic strategy for the treatment of ROS-related cardiac pathology including I/R injury.

DOI 10.1371/journal.pone.0189948
ISSN 1932-6203
Citation Morihara H, Obana M, Tanaka S, Kawakatsu I, Tsuchiyama D, Mori S, et al. 2-aminoethoxydiphenyl borate provides an anti-oxidative effect and mediates cardioprotection during ischemia reperfusion in mice. PLoS ONE. 2017;12(12):e0189948.

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