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Ashok 2023 Mol Cell Biochem

From Bioblast
Publications in the MiPMap
Ashok S, Raji SR, Manjunatha S, Srinivas G (2023) Impairment of substrate-mediated mitochondrial respiration in cardiac cells by chloroquine.

ยป Mol Cell Biochem [Epub ahead of print]. PMID: 37074504

Ashok Sivasailam, Raji Sasikala Rajendran, Manjunatha Shankarappa, Srinivas Gopala (2023) Mol Cell Biochem

Abstract: Chloroquine (CQ) has a long clinical history as an anti-malarial agent and also being used for the treatment of other infections and autoimmune diseases. Recently, this lysosomotropic agent and its derivatives are also been tested as adjuncts alongside conventional anti-cancer treatments in combinatorial therapies. However, their reported cardiotoxicity tends to raise concern over their indiscriminate use. Even though the influence of CQ and its derivatives on cardiac mitochondria is extensively studied in disease models, their impact on cardiac mitochondrial respiration under physiological conditions remains inconclusive. In this study, we aimed to evaluate the impact of CQ on cardiac mitochondrial respiration using both in-vitro and in-vivo model systems. Using high-resolution respirometry in isolated cardiac mitochondria from male C57BL/6 mice treated with intraperitoneal injection of 10 mg/kg/day of CQ for 14 days, CQ was found to impair substrate-mediated mitochondrial respiration in cardiac tissue. In an in-vitro model of H9C2 cardiomyoblasts, incubation with 50 ยตM of CQ for 24 h disrupted mitochondrial membrane potential, produced mitochondrial fragmentation, decreased mitochondrial respiration and induced superoxide generation. Altogether, our study results indicate that CQ has a deleterious impact on cardiac mitochondrial bioenergetics which in turn suggests that CQ treatment could be an added burden, especially in patients affected with diseases with underlying cardiac complications. As CQ is an inhibitor of the lysosomal pathway, the observed effect could be an outcome of the accumulation of dysfunctional mitochondria due to autophagy inhibition. โ€ข Keywords: Chloroquine, Heart, High-resolution respirometry, Metabolism, Mitochondria โ€ข Bioblast editor: Plangger M

Labels: MiParea: Respiration, Pharmacology;toxicology 

Organism: Mouse  Tissue;cell: Heart  Preparation: Isolated mitochondria 

Coupling state: OXPHOS  Pathway: F, N, S, NS, ROX  HRR: Oxygraph-2k