Oltipraz ameliorates pressure overload-induced pathological cardiac hypertrophy in mice.

Oltipraz (OPZ), a synthetic dithiothiol, is regarded as a novel agonist of nuclear factor erythroid-2 (Nrf-2). Recent studies revealed that Nrf-2 activation could suppress the pathological cardiac hypertrophy in mice. However, the therapeutic role of OPZ in the pathological cardiac hypertrophy remains incompletely understood. Thus, we evaluated the cardioprotective effects of OPZ in vivo and in vitro. Transverse aortic constriction (TAC) surgery was performed to induce the pathological cardiac hypertrophy in mice. In addition, the H9c2 cells were treated with angiotensin II (Ang II) to induce cardiomyocyte hypertrophy in vitro experiments. Our data revealed that OPZ relieved the TAC-induced pathological cardiac hypertrophy and myocardial damage in mice. Similarly, OPZ mitigated the increase in cardiomyocyte size induced by Ang II, indicating its ability to counteract cardiomyocyte hypertrophy. In addition, OPZ reduces cardiomyocyte oxidative stress, inflammation and apoptosis by activating Nrf-2 signaling in vivo and in vitro. Interestingly, our results also demonstrated that Nrf-2 knockdown abolished the protective effects of OPZ in vitro. Taken together, these data revealed that OPZ ameliorates the pathological cardiac hypertrophy via activating Nrf-2 signaling.