Open Access2-aminoethoxydiphenyl borate provides an anti-oxidative effect and mediates cardioprotection during ischemia reperfusion in mice
Author(s) -
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
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0189948
Subject(s) - cardioprotection , reactive oxygen species , intracellular , pharmacology , programmed cell death , extracellular , chemistry , reperfusion injury , microbiology and biotechnology , oxidative stress , ischemia , homeostasis , cytoprotection , medicine , biology , apoptosis , biochemistry
Excessive levels of reactive oxygen species (ROS) and impaired Ca 2+ 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 Ca 2+ 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 (H 2 O 2 ) -induced cell death by inhibiting the increase in intracellular Ca 2+ levels. However, no 2-APB-sensitive channel blocker inhibited H 2 O 2 -induced cell death and a direct reaction between 2-APB and H 2 O 2 was detected by 1 H-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.