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Curcumin, extracted from turmeric, has been found to relieve isoniazid\u2010induced hepatotoxicity. However, the mechanism of isoniazid\u2010induced hepatotoxicity and the protective effects of curcumin are not yet understood completely. We established both cell and animal models about isoniazid\u2010induced hepatotoxicity and investigated the new mechanism of curcumin against isoniazid\u2010induced liver injury. The experimental data in our study demonstrated that curcumin ameliorated isoniazid\u2010mediated liver oxidative stress. The protective effects of curcumin were demonstrated and confirmed to be correlated with upregulating SIRT1\/PGC\u20101\u03b1\/NRF1 pathway. Western blot revealed that while inhibiting SIRT1 by the siRNA1 (a SIRT1 inhibitor), the expressions of SIRT1, PGC\u20101\u03b1\/Ac\u2010PGC\u20101\u03b1, and NRF1 decreased, and the protective effect that curcumin exerted on isoniazid\u2010treated L\u201002 cells was significantly attenuated. Furthermore, curcumin improved liver functions and reduced necrosis of the isoniazid\u2010treated BALB\/c mice, accompanied by downregulating oxidative stress and inflammation in liver. Western blot revealed that curcumin treatment activates the SIRT1\/PGC\u20101\u03b1\/NRF1 pathway in the isoniazid\u2010treated BALB\/c mice. In conclusion, we found one mechanism of isoniazid\u2010induced hepatotoxicity downregulating the SIRT1\/PGC\u20101\u03b1\/NRF1 pathway, and curcumin attenuated this hepatotoxicity by activating it. Our study provided a novel approach and mechanism for the treatment of isoniazid\u2010induced hepatotoxicity.<\/jats:p>","DOI":"10.1002\/jat.4288","type":"journal-article","created":{"date-parts":[[2022,1,15]],"date-time":"2022-01-15T01:05:47Z","timestamp":1642208747000},"page":"1192-1204","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Curcumin attenuates isoniazid\u2010induced hepatotoxicity by upregulating the SIRT1\/PGC\u20101\u03b1\/NRF1 pathway"],"prefix":"10.1002","volume":"42","author":[{"given":"Yun","family":"Li","sequence":"first","affiliation":[{"name":"Department of Pharmacy The Second Xiangya Hospital, Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen\u2010wen","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy The Second Xiangya Hospital, Central South University  Changsha 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