ArticlePhysiological reports2015
High-dose chloroquine is metabolically cardiotoxic by inducing lysosomes and mitochondria dysfunction in a rat model of pressure overload hypertrophy.
Article in Physiological reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- Chloroquine and hydroxychloroquine are associated with reduced cardiovascular risk: a systematic review and meta-analysis.Drug design, development and therapy · 2018Pooled it
- The Interplay Between Autophagy and Porcine Epidemic Diarrhea Virus: From Molecular Mechanisms to Therapeutic Perspectives.Microorganisms · 2026Review
- Transcription factor, E4BP4, inhibits autophagy and apoptosis in multiple myeloma and promotes the HDAC3-mediated suppression of the Beclin1 promoter to reduce dexamethasone sensitivity.Journal of translational medicine · 2026Article
- Implications of ferritinophagy in cardiovascular diseases and its pharmacological modulation: underlying mechanisms and clinical translation strategies.Cellular & molecular biology letters · 2026Review
- Radiation-induced autophagy regulates fibroblast mitochondrial metabolism and crosstalk with triple-negative breast cancer cells.Cell reports · 2026Article
- Plekhm2 acts as an autophagy modulator in murine heart and cardiofibroblasts.Scientific reports · 2024Article
- Impairment of substrate-mediated mitochondrial respiration in cardiac cells by chloroquine.Molecular and cellular biochemistry · 2024Article
- Lipid emulsion inhibits the cardiac toxicity caused by chloroquine via inhibition of reactive oxygen species production.Korean journal of anesthesiology · 2023Article
- Hydroxychloroquine and azithromycin alter the contractility of living porcine heart slices.Frontiers in pharmacology · 2023Article
- Hydroxychloroquine Mitigates Dilated Cardiomyopathy Phenotype in Transgenic D94A Mice.International journal of molecular sciences · 2022Article
- Anti-malarial drugs: Mechanisms underlying their proarrhythmic effects.British journal of pharmacology · 2022Review
- Compromised mitochondrial quality control triggers lipin1-related rhabdomyolysis.Cell reports. Medicine · 2021Article
- Drug-induced organ injury in coronavirus disease 2019 pharmacotherapy: Mechanisms and challenges in differential diagnosis and potential protective strategies.Journal of biochemical and molecular toxicology · 2021Review
- Chloroquine and hydroxychloroquine in the treatment of COVID-19: the never-ending story.Applied microbiology and biotechnology · 2021Review
- Chronic inflammatory diseases, myocardial function and cardioprotection.British journal of pharmacology · 2020Review
- Double Jeopardy Cardiomyopathy Requiring Heart Transplant: Hydroxychloroquine and Rheumatoid Arthritis.CASE (Philadelphia, Pa.) · 2020Article
- Cardiac effects and toxicity of chloroquine: a short update.International journal of antimicrobial agents · 2020Review
- Dissecting pharmacological effects of chloroquine in cancer treatment: interference with inflammatory signaling pathways.Immunology · 2020Review
- The Effects of Chloroquine and Hydroxychloroquine on ACE2-Related Coronavirus Pathology and the Cardiovascular System: An Evidence-Based Review.Function (Oxford, England) · 2020Article
- Morphological Stages of Mitochondrial Vacuolar Degeneration in Phenylephrine-Stressed Cardiac Myocytes and in Animal Models and Human Heart Failure.Medicina (Kaunas, Lithuania) · 2019Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Autophagy, macroautophagy and chaperone-mediated autophagy (CMA), are upregulated in pressure overload (PO) hypertrophy. In this study, we targeted this process at its induction using 3 methyladenine and at the lysosomal level using chloroquine and evaluated the effects of these modulations on cardiac function and myocyte ultrastructure. Sprague-Dawley rats weighing 200 g were subjected to ascending aortic banding. After 1 week of PO, animals were randomized to receive 3 methyladenine versus chloroquine, intraperitoneally, for 2 weeks at a dose of 40 and 50 mg/kg/day, respectively. Saline injection was used as control. Chloroquine treatment, in PO, resulted in regression in cardiac hypertrophy but with significant impairments in cardiac relaxation and contractility. Ultrastructurally, chloroquine accentuated mitochondrial fragmentation and cristae destruction with a plethora of autophagosomes containing collapsed mitochondria and lysosomal lamellar bodies. In contrast, 3 methyladenine improved cardiac function and attenuated mitochondrial fragmentation and autophagososme formation. Markers of macroautophagy and CMA were significantly decreased in the chloroquine group; whereas 3 methyladenine treatment significantly attenuated macroautophagy with a compensatory increase in CMA. Furthermore, chloroquine accentuated PO induced oxidative stress through the further decrease in the expression of manganese superoxide dismutase; whereas, 3 MA had a completely opposite effect. Taken together, these data suggest that high-dose chloroquine, in addition to its effect on the autophagy-lysosome pathway, significantly impairs mitochondrial antioxidant buffering capacity and accentuates oxidative stress and mitochondrial dysfunction in PO hypertrophy; highlighting, the cautious administration of this drug in high oxidative stress conditions, such as pathological hypertrophy or heart failure.
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Registered trials
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