{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T02:24:28Z","timestamp":1786933468104,"version":"build-2736575974"},"reference-count":88,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,16]],"date-time":"2026-08-16T00:00:00Z","timestamp":1786838400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,16]],"date-time":"2026-08-16T00:00:00Z","timestamp":1786838400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Applied Toxicology"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Drug\u2010 and metal\u2010induced liver damage (DILI\/MILI) continues to be a predominant cause of acute hepatic failure globally, with two clinically significant but mechanistically underexplored triggers being the metalloid antimony (Sb) and non\u2010steroidal anti\u2010inflammatory medications (NSAIDs). This review consolidates current molecular findings about the convergence of Sb(III)\/Sb(V) species and NSAID reactive metabolites on a common hepatotoxic framework. Hepatic organic anion\u2010transporting polypeptides and multidrug\u2010resistance proteins regulate the sinusoidal uptake and canalicular efflux of both substances, while cytochrome P450 2C9\/3A4\/2E1\u2010mediated bioactivation of NSAIDs and thiol\u2010reactive Sb species produces reactive oxygen species (ROS), diminishes reduced glutathione (GSH) levels, disrupts mitochondrial membrane potential and initiates PERK\u2010eIF2\u03b1\u2010ATF4\u2010CHOP\u2010mediated endoplasmic reticulum stress. These insults target nuclear factor\u2010kappa B, mitogen\u2010activated protein kinase and NLRP3 inflammasome signalling, resulting in apoptotic, necroptotic, pyroptotic and ferroptotic hepatocyte death. We conduct a comprehensive assessment of the multi\u2010target hepatoprotective effects of polyphenols (curcumin, resveratrol, quercetin), flavonoids, terpenoids, alkaloids and extracts from medicinal plants, focusing on the activation of the Nrf2\/Keap1\/ARE antioxidant pathway, inhibition of NF\u2010\u03baB and NLRP3, AMPK\u2010SIRT1\u2010PGC\u20101\u03b1\u2010mediated mitochondrial biogenesis, PI3K\/Akt cytoprotective signalling and PINK1\/Parkin\u2010dependent mitophagy. We ultimately examine translational prospects, including omics\u2010derived hepatotoxicity biomarkers, network pharmacology, artificial intelligence\u2010facilitated natural product discovery, nanocarrier\u2010mediated hepatoprotective administration and precision medicine strategies for the prevention of drug\u2010induced liver injury (DILI). The intersection of antimony\u2010 and NSAID\u2010induced damage at a limited number of druggable targets supports the use of multi\u2010target natural therapies as logical complements to traditional hepatoprotection. However, the strength of evidence supporting this convergence is heterogeneous: Several downstream mechanisms\u2014particularly NLRP3 inflammasome activation, ferroptosis, pyroptosis and necroptosis in antimony\u2010induced hepatotoxicity\u2014are supported mainly by in\u00a0vitro and animal data rather than confirmed human evidence, and are treated in this review as emerging or hypothetical rather than established. As this is a narrative rather than a systematic review, the literature search strategy, evidence\u2010grading approach and limitations are described explicitly to aid transparent interpretation.<\/jats:p>","DOI":"10.1002\/jat.70395","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T01:45:32Z","timestamp":1786931132000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Antimony\u2010 and NSAID\u2010Induced Hepatotoxicity at the Molecular Crossroads: Redox, Inflammasome and Programmed Cell\u2010Death Networks as Therapeutic Targets for Natural Hepatoprotective Agents"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-5328-8606","authenticated-orcid":false,"given":"Shakir","family":"Siddiqui","sequence":"first","affiliation":[{"name":"Department of Pharmacology SDGI Global University  Ghaziabad Uttar Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5650-2146","authenticated-orcid":false,"given":"Neha Ronald","family":"William","sequence":"additional","affiliation":[{"name":"Department of Pharmacology SDGI Global University  Ghaziabad Uttar Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1765-5639","authenticated-orcid":false,"given":"Babita","family":"Aggarwal","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy SDGI Global University  Ghaziabad Uttar Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,16]]},"reference":[{"key":"e_1_2_18_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxrep.2022.03.011"},{"key":"e_1_2_18_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/10937404.2023.2261848"},{"key":"e_1_2_18_4_1","doi-asserted-by":"publisher","DOI":"10.4062\/biomolther.2024.188"},{"issue":"12","key":"e_1_2_18_5_1","first-page":"3315","article-title":"Mitochondrial Permeability Transition in Acetaminophen\u2010Induced Necrosis and Apoptosis of Cultured Mouse Hepatocytes","volume":"96","year":"2022","journal-title":"Archives of Toxicology"},{"key":"e_1_2_18_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2025.1524627"},{"key":"e_1_2_18_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms27031404"},{"key":"e_1_2_18_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/livers3010003"},{"key":"e_1_2_18_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418\u2010023\u201001187\u20100"},{"key":"e_1_2_18_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph17040520"},{"issue":"12","key":"e_1_2_18_11_1","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1080\/17425255.2023.2288260","article-title":"Review of Human Risk Factors for Idiosyncratic Drug\u2010Induced Liver Injury: Latest Advances and Future Goals","volume":"19","author":"Bj\u00f6rnsson H. 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