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

GONZÁLEZ ARBELÁEZ LF; CIOCCI PARDO, A; FANTINELLI JC; ROJANO B; SCHINELLA GR; MOSCA SM

NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY

SPRINGER

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 half an hour and re-established during 1 h. In the treated group, Isoesp was administered at the beginning of reperfusion. To assess the participation 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 was determined by triphenyl tetrazolium chloride staining technique. Post-ischemic recovery of contractility, oxidative stress, and content 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, and increased the expression of PKCε, Akt, and eNOS phosphorylated. All these beneficial effects achieved by Isoesp were annulled by 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.