Xanthine oxidase inhibition by allopurinol increases in vitro pyrazinamide-induced hepatotoxicity in HepG2 cells.
SourceDrug and Chemical Toxicology, 33, 3, (2010), pp. 325-328
1 juli 2010
Article / Letter to editor
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Drug and Chemical Toxicology
SubjectIGMD 2: Molecular gastro-enterology and hepatology; N4i 2: Invasive mycoses and compromised host; N4i 3: Poverty-related infectious diseases; NCEBP 13: Infectious diseases and international health; NCEBP 13: Infectious diseases and international health
Despite the important role of pyrazinamide in tuberculosis treatment, little is known about the mechanism of pyrazinamide-induced hepatotoxicity. We inhibited xanthine oxidase in HepG2 cells by using a nontoxic concentration of allopurinol, a well-known xanthine-oxidase inhibitor. This increased in vitro pyrazinamide toxicity in HepG2 cells, which suggests that the hydroxy metabolites of pyrazinamide are probably not fully responsible for pyrazinamide-induced toxicity, and that pyrazinoic acid and pyrazinamide are involved in pyrazinamide toxicity.
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