{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:51:56Z","timestamp":1781743916220,"version":"3.54.5"},"reference-count":391,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"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>Liver injury remains a significant global health concern with diverse etiologies including drug\u2010induced hepatotoxicity, chemical exposure, and metabolic disorders. Despite decades of research using animal models of liver injury, several critical gaps remain unaddressed in the literature. First, while individual models have been well described, there is no comprehensive, comparative framework that simultaneously evaluates classical hepatotoxin models, dietary models, and emerging systems (e.g., humanized mice, inflammation\u2010sensitized models, organoids) side\u2010by\u2010side. This fragmentation forces researchers to consult multiple disparate sources, leading to inconsistent model selection and reduced reproducibility. Second, the translational validity of these models\u2014particularly for idiosyncratic drug\u2010induced liver injury (iDILI), non\u2010alcoholic steatohepatitis (NASH), and herb\u2010induced liver injury (HILI)\u2014remains poorly benchmarked against human disease. Third, there is no evidence\u2010based decision framework that guides researchers toward the most appropriate model for a given mechanistic or therapeutic question (e.g., \u201cWhich model best recapitulates mitochondrial hepatotoxicity?\u201d or \u201cHow can I model immune\u2010mediated DILI?\u201d). Fourth, recent advances in omics technologies (single\u2010cell RNA sequencing, spatial transcriptomics, proteomics) and humanized platforms have not been systematically integrated into traditional model comparisons. This review aims to close these four gaps by providing a side\u2010by\u2010side comparative analysis of 18 distinct animal models across 12 parameters (induction method, injury pattern, mechanism, species\/strain differences, time course, regenerative response, advantages, limitations, translational relevance, cost, throughput, and ethical considerations), mapping each model to its closest human disease correlate with explicit discussion of similarities and limitations, proposing a practical, decision\u2010tree\u2010based model selection framework and integrating emerging technologies (humanized mice, CRISPR screens, organoids) into the classical landscape. Understanding the distinctive features of each model is essential for translational relevance and reproducibility in hepatotoxicity research.<\/jats:p>","DOI":"10.1002\/jat.70268","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:04:39Z","timestamp":1781741079000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparative Analysis of Classical and Emerging Experimental Animal Models of Liver Injury: A Comprehensive Review"],"prefix":"10.1002","author":[{"given":"Ibtehal Nasser","family":"Salman","sequence":"first","affiliation":[{"name":"Department of Pharmacy Alamal College for Specialized Medical Sciences  Karbala Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roaa Khaled","family":"Jabbar","sequence":"additional","affiliation":[{"name":"Department of Anesthesia Techniques Al\u2010Safwa University College  Karbala Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Israa","family":"Emad","sequence":"additional","affiliation":[{"name":"Pharmacology and Toxicology Department, College of Pharmacy University of Baghdad  Baghdad Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zain Al\u2010Abidin Ahmed","family":"Hassan","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Alamal College for Specialized Medical Sciences  Karbala Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abeer Mahdi","family":"Harbi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Alamal College for Specialized Medical Sciences  Karbala Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aseel Yass","family":"Khudhair","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Alamal College for Specialized Medical Sciences  Karbala Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malak Ali Mohammed","family":"Hussein","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Alamal College for Specialized Medical Sciences  Karbala Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali Majid","family":"Hamid","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Alamal College for Specialized Medical Sciences  Karbala Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahdi Abd","family":"Al Amir","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Alamal College for Specialized Medical Sciences  Karbala Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustafa Wafi","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Alamal College for Specialized Medical Sciences  Karbala Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8146-993X","authenticated-orcid":false,"given":"Mohamed M.","family":"Khalifa","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Alamal College for Specialized Medical Sciences  Karbala Iraq"},{"name":"Pharmaceutical Medicinal Chemistry &amp; Drug Design Department, Faculty of Pharmacy (Boys) Al\u2010Azhar University  Nasr City Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,17]]},"reference":[{"issue":"1","key":"e_1_2_17_2_1","doi-asserted-by":"crossref","DOI":"10.1186\/s40659-024-00510-4","article-title":"The Hepatoprotective Effect of 4\u2010Phenyltetrahydroquinolines on Carbon Tetrachloride Induced Hepatotoxicity in Rats Through Autophagy Inhibition","volume":"57","author":"Abdelgalil M. 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