{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:09:28Z","timestamp":1787018968109,"version":"build-2736575974"},"reference-count":76,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2017,4,20]],"date-time":"2017-04-20T00:00:00Z","timestamp":1492646400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Hum Exp Toxicol"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:p>\n                    Pyrazinamide (PYZ)\u2014an essential component of primary drug regimen used for the treatment and management of multidrug resistant or latent tuberculosis\u2014is well known for its hepatoxicity. However, the mechanism of PYZ-induced hepatotoxicity is still unknown to researchers. Studies have shown that the drug is metabolized in the liver to pyrazinoic acid (PA) and 5-hydroxy pyrazinoic acid (5-OHPA) which individually may cause different degrees of hepatotoxicity. To evaluate this hypothesis, PYZ, PA, and 5-OHPA were administered to albino Wistar rats orally (respectively, at 250, 125, and 125 mg kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    for 28 days). Compared to normal rats, PYZ and its metabolic products decreased the weights of dosed rats and induced liver injury and a status of oxidative stress as assessed by combined histopathological and biochemical analysis. Compared to normal controls, the biochemical and morphological changes were more aberrant in PA- and 5-OHPA-dosed rats with respect to those dosed with PYZ. Finally, the serum metabolic profiles of rats dosed with PYZ, PA, and 5-OHPA were measured and compared with those of normal control rats. With respect to normal control rats, the rats dosed with PYZ and 5-OHPA showed most aberrant metabolic perturbations in their sera as compared to those dosed with PA. Altogether, the study suggests that PYZ-induced hepatotoxicity might be associated with its metabolized products, where 5-OHPA contributes to a higher degree in its overall toxicity than PA.\n                  <\/jats:p>","DOI":"10.1177\/0960327117705426","type":"journal-article","created":{"date-parts":[[2017,4,20]],"date-time":"2017-04-20T07:23:54Z","timestamp":1492673034000},"page":"373-389","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":32,"title":["Metabolomics approach discriminates toxicity index of pyrazinamide and its metabolic products, pyrazinoic acid and 5-hydroxy pyrazinoic acid"],"prefix":"10.1177","volume":"37","author":[{"given":"A","family":"Rawat","sequence":"first","affiliation":[{"name":"Department of Biotechnology, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Lucknow, Uttar Pradesh, India"},{"name":"Centre of Biomedical Research (CBMR), Sanjay Gandhi Post-Graduate Institute of Medical 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