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Drug-induced mitochondrial toxicity

Abstract : Mitochondrial dysfunction can be a major mechanism whereby different drugs can induce adverse effects affecting different tissues such as liver, heart and skeletal muscle. In the most severe cases, drug-induced mitochondrial dysfunction can require a hospitalization, or lead to the death of the patient. Moreover, these adverse effects can lead to the withdrawal of drugs from the market, or earlier during clinical trials. Drugs can induce mitochondrial dysfunction by different mechanisms including inhibition of fatty acid oxidation, impairment of oxidative phosphorylation and respiratory chain activity as well as alteration of the integrity of the mitochondrial membranes. Some drugs also impair mitochondrial function via the production of reactive oxygen species and the generation of reactive metabolites, which can covalently bind to key mitochondrial proteins. The present chapter focuses on different drugs for which enough clinical and experimental evidence indicates the potential role of mitochondrial dysfunction in the pathogenesis of adverse effects such as liver injury, myopathy and cardiotoxicity acetaminophen, amiodarone, doxorubicin, nucleoside reverse transcriptase inhibitors (e.g. stavudine, zidovudine, didanosine), statins (e.g. atorvastatin, cerivastatin, simvastatin) and valproic acid. Notably, these drugs epitomize the diversity of the mechanisms whereby xenobiotics can induce mitochondrial dysfunction and also the variety of the targeted tissues. Other drugs affecting mitochondrial function by similar mechanisms are discussed more briefly in the present chapter. Because drug-induced mitochondrial dysfunction and related adverse events are major issues for public health and pharmaceutical companies, mitochondrial liability should be systematically investigated during preclinical safety studies. © Springer International Publishing AG, part of Springer Nature 2018.
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Contributor : Laurent Jonchère Connect in order to contact the contributor
Submitted on : Wednesday, June 6, 2018 - 4:03:52 PM
Last modification on : Monday, January 10, 2022 - 3:11:53 PM



J. Massart, A. Borgne-Sanchez, B. Fromenty. Drug-induced mitochondrial toxicity. Drug-induced mitochondrial toxicity, Springer International Publishing, pp.269-295, 2018, 9783319733449; 9783319733432. ⟨10.1007/978-3-319-73344-9_13⟩. ⟨hal-01809329⟩



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