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Cardioprotective action of aprepitant in a rat model of ischemia-reperfusioninduced myocardial injury: role of PI3K-AkT-GSK-3ß-HIF-1α signaling pathway

Qian, Mei; Liu, Yang.
Acta cir. bras; 37(10): e371004, 2022. graf, tab
Artigo em Inglês | VETINDEX | ID: biblio-1415430

Resumo

Purpose: The present study explored the role and mechanism involved in aprepitant-induced cardioprotective effects in rat model of ischemia-reperfusion injury. Methods: The isolated hearts of Wistar male albino rats were subjected to ischemia-reperfusion injury on Langendorff apparatus. The extent of myocardial injury was assessed by measuring lactate dehydrogenase 1 and CK-MB release in the coronary effluent. The rats were treated with aprepitant (5, 10 and 20 mg/kg) before isolating hearts. After injury, the levels of HIF-1α, p-AkT, p-GSK-3ß/GSK-3ß were measured in heart homogenates. LY294002 was employed as PI3K inhibitor. Results: Ischemia-reperfusion led to significant myocardial injury and decreased the levels of HIF-1α, p-AkT and ratio of p-GSK-3ß/GSK-3ß. Aprepitant attenuated myocardial injury and restored the biochemical changes in a dose-dependent manner. Pre-treatment with LY294002 (10 and 20 mg/kg) abolished aprepitant-mediated cardioprotective effects and restored the biochemical parameters in the heart homogenate. Conclusions: Aprepitant may be effective in preventing ischemia-reperfusion-induced myocardial injury, which may be due to activation of PI3K-AkT-GSK-3ß and HIF-1α signaling pathway.
Biblioteca responsável: BR68.1
Localização: BR68.1