Hepatocellular toxicity of benzbromarone: Effects on mitochondrial function and structure

• Published in: Toxicology (Amsterdam) Vol. 324; pp. 136 - 146
• Main Authors: Felser, Andrea, Lindinger, Peter W, Schnell, Dominik, Kratschmar, Denise V, Odermatt, Alex, Mies, Suzette, Jenö, Paul, Krähenbühl, Stephan
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 03.10.2014
• Subjects: Adenosine Triphosphate - metabolism; Animals; Apoptosis; Apoptosis - drug effects; ATP; Benzbromarone; Benzbromarone - toxicity; Cellular; Chemical and Drug Induced Liver Injury - etiology; Chemical and Drug Induced Liver Injury - metabolism; Chemical and Drug Induced Liver Injury - pathology; Dose-Response Relationship, Drug; Emergency; Energy Metabolism - drug effects; Enzymes; Glycolysis - drug effects; Hep G2 Cells; Human; Humans; Lactic Acid - metabolism; Liver - drug effects; Liver - metabolism; Liver - pathology; Male; Mice; Mice, Inbred C57BL; Mitochondria; Mitochondria, Liver - drug effects; Mitochondria, Liver - metabolism; Mitochondria, Liver - pathology; Mitochondrial fragmentation; Mitochondrial toxicity; Molecular structure; Necrosis; Reactive Oxygen Species - metabolism; Respiratory chain; Time Factors; Toxicity; β-oxidation; β-oxidation; Respiratory chain; Benzbromarone; Mitochondrial toxicity; Mitochondrial fragmentation
• ISSN: 0300-483X; 1879-3185
• DOI: 10.1016/j.tox.2014.08.002

Highlights • Benzbromarone impairs the electron transport chain and uncouples mitochondria. • Benzbromarone impairs mitochondrial β-oxidation by inhibiting fatty acid activation. • Benzbromarone disrupts the mitochondrial network and induces apoptosis.