Pyrazinamide-induced hepatotoxicity and gender differences in rats as revealed by a ¹H NMR based metabolomics approach.

ABSTRACT: Pyrazinamide (PZA) is a well-known first line anti-tuberculosis drug used in combination with other drugs such as isoniazid and rifampicin. Unfortunately, PZA suffered from a high rate of hepatotoxicity and hyperuricemia, which has not been clearly elucidated, hindering its wide application for therapeutic purposes. The purpose of this investigation was to develop a model of rat sub-acute hepatotoxicity induced by PZA and to explore the affected metabolic pathways by a ¹H NMR-based metabolomics approach complemented with histopathological analysis and clinical chemistry. Rats of both genders were administered with PZA by gavage at doses of 1.0 and 2.0 g kg^-1 for 4 weeks. PZA decreased the weights of dosed rats and induced liver injury dose-dependently. The female rats

SUBMITTER: Zhao H 

PROVIDER: S-EPMC6062402 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature