{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T16:44:52Z","timestamp":1790095492267,"version":"4.0.1"},"reference-count":58,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T00:00:00Z","timestamp":1769385600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T00:00:00Z","timestamp":1769385600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Isoniazid (INH), a widely used first\u2010line anti\u2010tubercular drug, has significant concern for the hepatotoxicity in humans induced by oxidative stress, inflammation and steatosis. INH activates NLRP3 inflammasome and inhibits Nrf2 activation pathways. Isoliquiritigenin (ISO), a bioactive flavonoid, possesses antioxidant and anti\u2010inflammatory characteristics and responsible for the hepatoprotection in several experimental models. Male SD rats were assigned into six groups: control, ISO per se (20\u2009mg\/kg, p.o.), INH (50\u2009mg\/kg, p.o.), INH\u2009+\u2009ISO\u2010 low dose (5\u2009mg\/kg, p.o.), mid dose (10\u2009mg\/kg, p.o.), and high dose (20\u2009mg\/kg, p.o.). Hepatotoxicity was evaluated using different parameters such as SGPT, SGOT, ALP, GGT, bilirubin, oxidative stress such as MDA, CAT, GSH, inflammation by evaluating NLRP3 expression, fibrosis by measuring collagen deposition as well as histological assessment. INH treatment significantly perturbed the liver enzymes, oxidative stress indicators, while decreased the endogenous antioxidants. Histopathological examination confirmed liver damage, which included inflammation, steatosis, and fibrosis. ISO co\u2010administration significantly reduced these changes by restoring the antioxidant defense mechanisms, decreasing inflammatory mediators, and suppressing fibrotic changes. ISO significantly reduced INH\u2010induced hepatotoxicity by regulating the oxidative stress, inflammation, and steatosis pathways. Based on the mechanism of Nrf2 activation and NLRP3 inhibition, the present results provide the evidence that ISO has the potential to restore the liver damage and can act as a novel therapeutic strategy for INH induced hepatotoxicity in humans.<\/jats:p>","DOI":"10.1002\/jbt.70717","type":"journal-article","created":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T21:16:50Z","timestamp":1769462210000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Isoliquiritigenin, Nrf2 Activator, and NLRP3 Inhibitor Protects Isoniazid\u2010Induced Hepatotoxicity in Sprague\u2010Dawley Rats: Studies on Oxidative Stress, Inflammation, DNA Damage, Ferroptosis, and Steatosis"],"prefix":"10.1002","volume":"40","author":[{"given":"Gurpreet","family":"Singh","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Facility for Risk Assessment and Intervention Studies National Institute of Pharmaceutical Education and Research  S.A.S Nagar Punjab India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Aabis","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Facility for Risk Assessment and Intervention Studies National Institute of Pharmaceutical Education and Research  S.A.S Nagar Punjab India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vaishali","family":"Maurya","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Facility for Risk Assessment and Intervention Studies National Institute of Pharmaceutical Education and Research  S.A.S Nagar Punjab India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinod","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Facility for Risk Assessment and Intervention Studies National Institute of Pharmaceutical Education and Research  S.A.S Nagar Punjab India"},{"name":"Department of Pharmacology and Toxicology, High Resolution Transmission Electron Microscopy Facility National Institute of Pharmaceutical Education and Research  S.A.S Nagar Punjab India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9437-7252","authenticated-orcid":false,"given":"Gopabandhu","family":"Jena","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Facility for Risk Assessment and Intervention Studies National Institute of Pharmaceutical Education and Research  S.A.S Nagar Punjab India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,26]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2023.110439"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2015.06.020"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2024.1389684"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1746.2012.07279.x"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2023.115861"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gendis.2021.12.006"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/8086253"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2018.02.037"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2025.111448"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.113968"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1109938"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2019.11.100"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.112594"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.3a0114-005rr"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2022.09.118"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.826204"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1395735"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-017-0895-5"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2010.09.001"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2014.12.043"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/CM9.0000000000002675"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbt.70408"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2022.154117"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40360-018-0201-x"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2024.103406"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2014.10.030"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2025.157436"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-018-1540-2"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12011-022-03392-3"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1080\/01480545.2016.1188398"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2022.153256"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbt.22476"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-025-04143-6"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2018.00198"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2025.1551003"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2020.09.140"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2006.01.027"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.3109\/01480545.2015.1092039"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1080\/00498254.2025.2497050"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01639-18"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chemosphere.2019.04.026"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpc.2022.109430"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-79016-8"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbt.23492"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2024.05.012"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1111\/gtc.13108"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.3109\/15376511003793325"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2024.111160"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12885"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.7101"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00394-015-1051-6"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2022.115368"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.4196\/kjpp.2018.22.4.369"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.128.1.116"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.13795"},{"key":"e_1_2_12_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2010.355"},{"key":"e_1_2_12_58_1","doi-asserted-by":"publisher","DOI":"10.1111\/fcp.12157"},{"key":"e_1_2_12_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.LIVRES.2021.02.001"}],"container-title":["Journal of Biochemical and Molecular Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbt.70717","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jbt.70717","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbt.70717","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T09:32:36Z","timestamp":1771234356000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jbt.70717"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,26]]},"references-count":58,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["10.1002\/jbt.70717"],"URL":"https:\/\/doi.org\/10.1002\/jbt.70717","archive":["Portico"],"relation":{},"ISSN":["1095-6670","1099-0461"],"issn-type":[{"value":"1095-6670","type":"print"},{"value":"1099-0461","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,26]]},"assertion":[{"value":"2025-09-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70717"}}