[Mitochondrial toxicity of drugs].
Considering the complexity of mitochondria, it is not surprising that the pathogenesis of adverse drug events often develop on drug-induced mitochondrial injury. Drug induced mitochondrial toxicity can occur through several mechanisms, such as depletion of mtDNA (e.g. NRTI), inhibition of fatty acid beta-oxidation (e.g. valproic acid), opening of the mitochondrial permeability transition pore (e.g. anthracyclines), formation of mitochondrial oxidative stress and depletion of mitochondrial glutathione pool (e.g. acetaminophen), uncoupling of electron transport from ATP synthesis (e.g. tamoxifen) and inhibition of mitochondrial electron transport chain complexes (e.g. simvastatin). This review focuses on the mitochondrial toxicity of drugs in general and explains the practical relevance of these adverse drug events according to specific drugs (metformin, statins, acetaminophen, valproic acid). Furthermore the significance of mitotropic micronutrients such as coenzyme Q10, L-carnitine and glutathione in the prevention and management ofdrug-induced mitochondrial injury is discussed.
Akademie & Zentrum für Mikronährstoffmedizin, Zweigertstrasse 55, 45130 Essen. uwegroeber@gmx.net
Uwe
U
Gröber
D000818:Animals; D004272:DNA, Mitochondrial / Q000187:drug effects; D064420:Drug-Related Side Effects and Adverse Reactions; D004579:Electron Transport / Q000187:drug effects; D006801:Humans; D008928:Mitochondria / Q000187:drug effects*; D028361:Mitochondrial Diseases / Q000139:chemically induced*; D033681:Mitochondrial Membrane Transport Proteins / Q000187:drug effects; D000083162:Mitochondrial Permeability Transition Pore
D004272:DNA, Mitochondrial; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore