Participation of mitochondria in the cardioprotective effect mediated by 6-ethoxyzolamide

ALEJANDRO CIOCCI PARDO; LUISA F GONZÁLEZ ARBELÁEZ; SUSANA M MOSCA

Congreso; Reunión anual SAFIS; 2020

Previous data from our laboratory show that AC inhibition with 6-ethoxyzolamide (ETX) reduces the infarct size and improves the post-ischemic recovery of myocardial function, however the participation of mitochondria, key actors in the injury associated to I/R, has not been clarified yet. The objective of this work was to study the effects of AC blockade with ETX on mitochondrial alterations produced by IR. Isolated hearts from Wistar rats, perfused by the Langendorff technique and after 20 min of stabilization (E), were assigned to the following groups: 1) Control (C): they were perfused until completing 110 min; 2) Ischemic control (IC): 30 min of global ischemia and 60 min of reperfusion (R); 3) ETX: 100 μM ETX was administered during the last 10 min of E and the first 10 min of R. To evaluate the participation of p38MAPK and PKCε, experiments were carried out in the presence of their inhibitors SB202190 (10 μM) and chelerythrin (Che) (1 μM), respectively, those administered during the first 10 min of R. Mitochondrial state was determined by changes in light scattering (ΔDL) by the addition of 200 μM Ca2+, Ca2+ retention capacity of (CRC, Calcium Green 5N) and membrane potential (ΔΨm, Rhodamine-123) in isolated mitochondria from the different groups. Mitochondrial fission was evaluated through the content of Ser637-P-Drp1 by western blot (WB). The content of P-p38MAPK, P-PKCε, Calcineurin Aβ, P-HSP27 was also evaluated by WB. ETX increased ΔDL (1.26 ± 0.2 vs 0.3 ± 0.1 u.a), CRC (266 ± 10 vs 5 ± 1 nmol / mg protein) and preserved ΔΨm (-141 ± 5 vs -95 ± 6 mV) (p