Thioredoxin 1 is required for the cardioprotective effect of sildenafil against ischemia-reperfusion injury and mitochondrial dysfunction in mice

ZAOBORNYJ T; GOMEZ A; D´ANNUNZIO V; MAZO T; CASANOVA V; PEREZ V; CICALE E; GELPI RJ

Congreso; LXIII Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2018

Sociedad Argentina de Investigación Clínica (SAIC)

Sildenafil is a phosphodiesterase type 5 inhibitor indicated in erectile dysfunction and pulmonary hypertension, which confers cardioprotection against myocardial ischemia/reperfusion (I/R) injury. Thioredoxin-1 (Trx1) is a protein which contains redox-sensitive cysteine residues and acts as an antioxidant in cells. The aim of this study was to determine if Trx1 system participates in cardioprotection exerted by sildenafil in an acute model of I/R, and to evaluate mitochondrial bioenergetics. Langendorff-perfused hearts from wild type mice (WT) and a dominant negative (DN-Trx1) mutant (C32S/C35S) of Trx1 were assigned to placebo or sildenafil (0.7 mg/kg i.p.) and subjected to 30 min of ischemia followed by 120 min of reperfusion. WT mice treated with sildenafil showed a significantly smaller (41%) infarct size. This protective effect was not observed when sildenafil treatment was administered to DN-Trx1 mice. After I/R, treatment with sildenafil preserved state 3 oxygen consumption from WT mice (137.9±7.6 vs. 140.9±11.0, P