Cardioprotective effects of chloroquine pretreatment on ischemic and reperfusion injury via activation of ERK1/2 in isolated rat hearts.

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.

• Authors: Ryota Murase, Yasushige Shingu, Satoru Wakasa
• Journal: Molecular biology reports (Mol Biol Rep) Vol. 49 Issue 10 Pg. 9429-9436 (Oct 2022) ISSN: 1573-4978 [Electronic] Netherlands
• PMID: 35896843 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s), under exclusive licence to Springer Nature B.V.

Chemical References

• Chloroquine
• Proto-Oncogene Proteins c-akt
• Extracellular Signal-Regulated MAP Kinases

Topics

• Animals
• Chloroquine (pharmacology)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• MAP Kinase Signaling System (physiology)
• Myocardial Reperfusion Injury (metabolism)
• Phosphorylation
• Proto-Oncogene Proteins c-akt (metabolism)
• Rats
• Reperfusion Injury