Research advances in hepatotoxicity mechanism of benzbromarone

Benzbromarone is a potent uricosuric drug by inhibiting the re-absorption of uric acid salt in renal proximal convoluted tubules and widely used for gout and hyperuricemia. The common adverse reactions of benzbromarone are gastrointestinal symptoms (including diarrhea, stomach discomfort, and nausea), skin allergies (including rash and itching), and abnormal liver function with the increase of aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase. Hepatotoxicity induced by benzbro-marone is mainly associated with the suppression of β-oxidation and respiratory chain, reducing the synthesis of ATP, increasing the generation of reactive oxygen species, promoting the opening of mitochondrial permeability transition pore and leading to apoptosis induced by the release of cytochrome C. In addition, the synthesis of adjacent benzene ortho-quinone intermediate and the decrease of glutathione, level could exacerbate hepatotoxicity. Cytochrome P450(CYP) oxidase is important for metabolism of benzbromarone and increase of the activity of CYP2C9/CYP3A4 and CYP2C9*3 mutation are likely to increase the hepa-totoxicity of benzbromarone. Key words: Benzbromarone; Drug-induced liver injury