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Τετάρτη 27 Ιανουαρίου 2021

Aloin antagonizes stimulated ischemia/reperfusion-induced damage and inflammatory response in cardiomyocytes by activating the Nrf2/HO-1 defense pathway

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Abstract

Myocardial ischemia/reperfusion injury (I/RI) frequently incurs in acute myocardial infarction with high morbidity and mortality worldwide and is characterized with cardiomyocyte apoptosis and inflammatory response. Aloin is a major anthraquinone from Aloe species and fulfills pleiotropic protective functions in several disease models including hepatic injury. Nevertheless, the potential of aloin in MI/RI remains elusive. Intriguingly, aloin had modest cytotoxicity in H9c2 cardiomyocytes. Importantly, aloin dose-dependently ameliorated cell viability that was inhibited in response to simulated ischemia/reperfusion (SI/R) stimulation. Moreover, the enhanced apoptosis in cells under SI/R conditions were reduced after aloin treatment, concomitant with the decrease in pro-apoptotic Bax protein levels and increase in anti-apoptotic Bcl-2 protein expression. Of interest, aloin administration attenuated SI/R-induced oxidant stress by decreasing reactive oxygen species (ROS) production, lactate dehydrogenase (LDH), and malondialdehyde (MDA) release and increasing activity of anti-oxidant stress enzyme superoxide dismutase (SOD). Additionally, the elevated pro-inflammatory cytokine levels were counteracted after aloin treatment in cells under SI/R conditions, including TNF-α, IL-6, and IL-1β. Mechanically, aloin further enforced the activation of the NF-E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling. Noticeably, blockage of this pathway by si-Nrf2 transfection blunted aloin-mediated cardioprotective efficacy against SI/R-evoked oxidative stress injury and inflammatory response. Thus, these findings corroborate that aloin may antagonize SI/R-induced cardiomyocyte injury by attenuating excessive oxidative stress and inflammation, thereby endorsing its potential as a promising therapeutic agent against myocardial infarction.

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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