Cardioprotective Effects of Chloroquine Pretreatment on Ischemic and Reperfusion Injury Via Activation of ERK1/2 in Isolated Rat Hearts

Overview

Journal Mol Biol Rep

Specialty Molecular Biology

Date 2022 Jul 27

PMID 35896843

Authors

Ryota Murase

Yasushige Shingu

Satoru Wakasa

Affiliations

Soon will be listed here.

Abstract

Purpose: Several therapeutic agents have been found to prevent myocardial ischemic and reperfusion (I/R) injury after cardiac surgery; however, no drug is routinely used to afford cardioprotective benefits in clinical settings. Herein, we aimed to determine whether chloroquine (CQ) pretreatment attenuates I/R injury after global ischemia in isolated rat hearts and elucidate mechanisms underlying the effects of CQ.

Methods: Isolated rat hearts were subjected to 30-min global ischemia, followed by 60-min reperfusion with Krebs-Henseleit buffer (KHB). Immediately before ischemia, 10 mL of pretreatment solutions (KHB, n = 4 or KHB + CQ [100 μM], n = 4) were injected through the aortic root. Cardiac function was examined based on the rate pressure product (RPP). Myocardial apoptosis was evaluated using TUNEL staining. To assess the reperfusion ischemia salvage kinase pathway, protein expression levels of AKT and extracellular signal-regulated kinase (ERK1/2) were determined using western blotting. To investigate the role of ERK1/2, an ERK1/2 selective inhibitor was used in eight additional rats.

Results: The recovery rate of the RPP was higher in the KHB + CQ group than in the KHB group 60 min after I/R (KHB, 44 ± 3% vs. KHB + CQ, 69 ± 7%; P = 0.019, d = 2.2). CQ pretreatment reduced apoptosis and enhanced the phosphorylation of ERK1/2; however, AKT phosphorylation was unaltered. In addition, the ERK1/2 inhibitor abolished CQ-mediated cardioprotective effects.

Conclusions: CQ pretreatment showed protective effects on cardiac function after I/R by activating ERK1/2.

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