Revisiting the Cardiotoxic Effect of Chloroquine
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Cardiotoxicity is a well-known side effect of chloroquine. Several studies have proposed chloroquine as a potential anti-diabetic treatment but do not address this problem. The current study investigated the effect of ex vivo chloroquine treatment on (1) heart function and glucose uptake, (2) mitochondrial function and (3) in vivo treatment on heart function.
Control or obese male Wistar rats were used throughout. Dose responses of increasing chloroquine concentrations versus vehicle on cardiac function were measured using isolated, Langendorff-perfused hearts whilst glucose uptake and cell viability were determined in ventricular cardiomyocytes. Mitochondrial function was assessed with a Clark-type oxygraph (Hansatech) after ex vivo perfusion with 30 μM chloroquine versus vehicle. Animals were treated orally with 5 mg/kg/day chloroquine for 6 weeks.
Acute chloroquine treatment of 10 μM was sufficient to significantly decrease heart function (p < 0.05) whilst 30 μM significantly reduced heart rate (p < 0.05). Chloroquine became toxic to isolated cardiomyocytes at high concentrations (100 μM), and had no effect on cardiomyocyte glucose uptake. Ex vivo treatment did not affect mitochondrial function, but chronic low-dose in vivo chloroquine treatment significantly decreased aortic output and total work in hearts (p < 0.005).
Low and intermediate chloroquine doses administered either chronically or acutely are sufficient to result in myocardial dysfunction.
KeywordsChloroquine Cardiotoxicity Mitochondrial dysfunction Insulin resistance Diabetes
We acknowledge funding from the South African National Research Foundation.
Compliance with Ethical Standards
All applicable international, national, and institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution at which the studies were conducted. This study was approved by the Stellenbosch University Research Ethics Committee: Animal Care and Use (Protocol number SU-ACUM12-00040; SU-ACUD16-0079) and complied with the accepted national and international standards for the use of animals in research as stipulated in the South African National Standards 10386: 2008. This article does not contain any studies with human participants performed by any of the authors.
Conflict of Interest
The authors declare that they have no conflict of interest.
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