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

ZAOBORNYJ, TAMARA; MAZO, TAMARA; GOMEZ, ANABELLA; PEREZ, VIRGINIA; D' ANNUNZIO V; GELPI, RICARDO J.

Congreso; IV International Congress inTranslational Medicine; 2018

Sildenafil is a phosphodiesterase type 5 inhibitor indicated in erectiledysfunction and pulmonary hypertension, which confers cardioprotection againstmyocardial ischemia/reperfusion (I/R) injury. Thioredoxin-1 (Trx1) is a proteinwhich contains redox-sensitive cysteine residues and acts as an antioxidant incells. The aim of this study was to determine if Trx1 system participates incardioprotection exerted by sildenafil in an acute model of I/R, and toevaluate mitochondrial bioenergetics. Langendorff-perfused hearts from wildtype mice (WT) and a dominant negative (DN-Trx1) mutant (C32S/C35S) of Trx1 wereassigned to placebo or sildenafil (0.7 mg/kg i.p.) and subjected to 30 min ofischemia 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 treatmentwas administered to DN-Trx1 mice. After I/R, treatment with sildenafilpreserved state 3 oxygen consumption from WT mice (137.9±7.6 vs. 140.9±11.0,P