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

Hirofumi Morihara, Masanori Obana, Shota Tanaka, Ikki Kawakatsu, Daisuke Tsuchiyama, Shota Mori, Hiroshi Suizu, Akiko Ishida, Rumi Kimura, Izuru Tsuchimochi, Makiko Maeda, Takehiko Yoshimitsu, Yasushi Fujio, Hiroyuki Nakayama

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2 Citations (Scopus)

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.

Original languageEnglish
Article numbere0189948
JournalPloS one
Volume12
Issue number12
DOIs
Publication statusPublished - Dec 2017

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    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. (2017). 2-aminoethoxydiphenyl borate provides an anti-oxidative effect and mediates cardioprotection during ischemia reperfusion in mice. PloS one, 12(12), [e0189948]. https://doi.org/10.1371/journal.pone.0189948