{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T01:29:17Z","timestamp":1789003757469,"version":"build-2803163510"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2021,4,1]],"date-time":"2021-04-01T00:00:00Z","timestamp":1617235200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Anti-TB drugs-isoniazid and rifampicin induced hepatotoxicity present a significant clinical problem. We aimed to evaluate the beneficial effect of gallic acid in anti-TB drug-induced liver injury in vivo and for the mechanism of action, we explored the influence of gallic acid on Nrf2 and NF-\u03baB pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We assessed serum liver function tests and histopathological analysis for the preventive effect of gallic acid on liver injury. For exploring the beneficial mechanism, we studied Nrf2 and NF-\u03baB signalling pathways using molecular assays. Subsequently, we conducted in vitro cytotoxicity assays with Nrf2(ML385) and NF-\u03baB(BAY 11\u20137085) antagonists.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key findings<\/jats:title>\n                    <jats:p>Gallic acid co-administration attenuated the elevation of liver function enzymes, hepatic necrosis and inflammation compared to the anti-TB drug treatment alone. Mechanistic investigations reveal that gallic acid increased Nrf2 activation and induction of its downstream targets, preventing cytotoxicity by isoniazid and rifampicin. The protective effect of gallic acid diminished in the presence of Nrf2 antagonists in vitro. Furthermore, we found that gallic acid treatment inhibited NF-\u03baB\/TLR-4 axis upregulated by the anti-TB drugs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Gallic acid is effective in preventing isoniazid and rifampicin induced hepatotoxicity in vivo by improving the redox homeostasis by activating Nrf2 and inhibiting NF-\u03baB signalling pathways.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jpp\/rgaa048","type":"journal-article","created":{"date-parts":[[2020,12,31]],"date-time":"2020-12-31T23:13:53Z","timestamp":1609456433000},"page":"473-486","source":"Crossref","is-referenced-by-count":53,"title":["Gallic acid attenuates isoniazid and rifampicin-induced liver injury by improving hepatic redox homeostasis through influence on Nrf2 and NF-\u03baB signalling cascades in Wistar Rats"],"prefix":"10.1093","volume":"73","author":[{"given":"Sukumaran","family":"Sanjay","sequence":"first","affiliation":[{"name":"Department of Pharmacology, JIPMER , Puducherry,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1777-5120","authenticated-orcid":false,"given":"Chandrashekaran","family":"Girish","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, JIPMER , Puducherry,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pampa Ch","family":"Toi","sequence":"additional","affiliation":[{"name":"Department of Pathology, JIPMER , Puducherry,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachariah","family":"Bobby","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, JIPMER , Puducherry,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,4,1]]},"reference":[{"key":"2024103012055871600_CIT0001","first-page":"147","volume-title":"Treatment of Tuberculosis: Guidelines","author":"World Health Organisation","year":"2010","edition":"4th ed."},{"key":"2024103012055871600_CIT0002","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1111\/j.1440-1746.2007.05207.x","article-title":"Antituberculosis drug-induced hepatotoxicity: concise up-to-date review","volume":"23","author":"Tostmann","year":"2008","journal-title":"J Gastroenterol Hepatol"},{"key":"2024103012055871600_CIT0003","doi-asserted-by":"crossref","first-page":"2396","DOI":"10.1038\/ajg.2010.287","article-title":"Single-center experience with drug-induced liver injury from India: causes, outcome, prognosis, and predictors of mortality","volume":"105","author":"Devarbhavi","year":"2010","journal-title":"Am J 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