Isoespintanol, a monoterpene isolated from oxandra cf xylopioides, ameliorates the myocardial ischemia-reperfusion injury by AKT/PKCε/eNOS-dependent pathways

GONZÁLEZ ARBELÁEZ, LUISA F.; CIOCCI PARDO, ALEJANDRO; FANTINELLI, JULIANA C; ROJANO, BENJAMÍN; SCHINELLA, GUILLERMO R; MOSCA, SUSANA M

NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY

SPRINGER

Lugar: Germany; Año: 2019

0028-1298

Purpose To determine the actions of isoespintanol (Isoesp) on post-ischemic myocardial and mitochondrial alterations.Methods Hearts removed fromWistar rats were perfused by 20 min. After this period, the coronary flow was interrupted by halfan hour and re-established during 1 h. In the treated group, Isoesp was administered at the beginning of reperfusion. To assess theparticipation of ε isoform of protein kinase C (PKCε), protein kinase B (PKB/Akt), and nitric oxide synthase (NOS), hearts weretreated with Isoesp plus the respective inhibitors (chelerythrine, wortmannin, and N-nitro-L-argininemethyl ester). Cell death wasdetermined by triphenyl tetrazolium chloride staining technique. Post-ischemic recovery of contractility, oxidative stress, andcontent of phosphorylated forms of PKCε, Akt, and eNOS were also examined. Mitochondrial state was assessed through themeasurement of calcium-mediated response, calcium retention capacity, and mitochondrial potential.Results Isoesp limited cell death, decreased post-ischemic dysfunction and oxidative stress, improved mitochondrial state, andincreased the expression of PKCε, Akt, and eNOS phosphorylated. All these beneficial effects achieved by Isoesp were annulledby the inhibitors.Conclusion These findings suggest that activation of Akt/eNOS and PKCε signaling pathways are involved in the developmentof Isoesp-induced cardiac and mitochondria tolerance to ischemia-reperfusion.