{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T04:52:28Z","timestamp":1776142348972,"version":"3.50.1"},"reference-count":20,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T00:00:00Z","timestamp":1775865600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100032498","name":"Universidad Nacional Jorge Basadre Grohmann","doi-asserted-by":"crossref","award":["10570-2022-UNJBG"],"award-info":[{"award-number":["10570-2022-UNJBG"]}],"id":[{"id":"10.13039\/100032498","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diseases"],"abstract":"<jats:p>Background\/Objectives: Chemically induced hepatotoxicity is widely used in experimental research to model liver disease pathophysiology and to support preclinical studies. Thioacetamide (TAA) is a well-established hepatotoxic agent in conventional laboratory rodents; however, its effects in synanthropic rats\u2014characterized by genetic heterogeneity and chronic environmental exposure\u2014remain poorly defined. This study aimed to establish and characterize a preclinical model of TAA-induced hepatotoxicity in synanthropic rats and to assess its relevance for experimental liver disease research. Methods: Female synanthropic rats representing four phenotypic variants (albino, mottled, black, and brown; total n = 132) were housed under controlled conditions and assigned to control or TAA-treated groups. TAA was administered intraperitoneally at doses ranging from 200 to 300 mg\/kg. Clinical parameters, including body weight and vital signs, were periodically monitored. Hematological profiles and serum biochemical markers of liver function were analyzed. Hepatic injury was evaluated by histopathological examination using hematoxylin\u2013eosin staining. Statistical analyses were performed using R software, with p \u2264 0.05 considered statistically significant. Results: TAA-treated rats developed consistent clinical manifestations of hepatotoxicity, including progressive weight loss and reduced activity. Biochemical analyses revealed significant increases in serum transaminases, gamma-glutamyl transferase, and alkaline phosphatase, accompanied by alterations in hematological parameters. Histological evaluation demonstrated dose-dependent liver injury characterized by centrilobular necrosis, inflammatory infiltration, hepatocellular degeneration, and architectural disruption across all synanthropic rat variants. Conclusions: Synanthropic rats exhibit reproducible biochemical, hematological, and histopathological features of TAA-induced liver injury comparable to those reported in conventional laboratory strains. This model represents a robust preclinical approach for studying chemically induced hepatotoxicity and may provide enhanced translational relevance due to its genetic and environmental heterogeneity.<\/jats:p>","DOI":"10.3390\/diseases14040142","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T07:29:29Z","timestamp":1776065369000},"page":"142","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Establishment of a Thioacetamide-Induced Hepatotoxicity Model in Synanthropic Rats with Translational Relevance"],"prefix":"10.3390","volume":"14","author":[{"given":"Lesly Adelis","family":"Valdivia Quispe","sequence":"first","affiliation":[{"name":"Laboratory of Regenerative Medicine, Universidad Nacional Jorge Basadre Grohmann, Tacna 23003, Peru"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucio","family":"Velasco Lopez","sequence":"additional","affiliation":[{"name":"Laboratory of Regenerative Medicine, Universidad Nacional Jorge Basadre Grohmann, Tacna 23003, Peru"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daysi Zulema","family":"D\u00edaz Obreg\u00f3n","sequence":"additional","affiliation":[{"name":"Innovation and Science for the Care and Support of Society\u2014INNOVACARE, Lima 15024, Peru"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7372-2608","authenticated-orcid":false,"given":"Alexis German","family":"Murillo Carrasco","sequence":"additional","affiliation":[{"name":"Immunology and Cancer Research Group (IMMUCA), OMICS, Lima 15001, Peru"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joel","family":"de Le\u00f3n Delgado","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Research Center for Virology, Universidad de San Mart\u00edn de Porres, Lima 15001, Peru"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7534-8923","authenticated-orcid":false,"given":"Luis","family":"Lloja Lozano","sequence":"additional","affiliation":[{"name":"Laboratory of Regenerative Medicine, Universidad Nacional Jorge Basadre Grohmann, Tacna 23003, Peru"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jhon Wilfredo","family":"Pando Mayta","sequence":"additional","affiliation":[{"name":"Institute of Cryopreservation and Cell Therapy, Lima 15001, Peru"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1597-8370","authenticated-orcid":false,"given":"Anthony Brayan","family":"Rivera Prado","sequence":"additional","affiliation":[{"name":"Laboratory of Regenerative Medicine, Universidad Nacional Jorge Basadre Grohmann, Tacna 23003, Peru"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelly Geraldine","family":"Yparraguirre Salcedo","sequence":"additional","affiliation":[{"name":"Laboratory of Regenerative Medicine, Universidad Nacional Jorge Basadre Grohmann, Tacna 23003, Peru"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V\u00edctor Hugo","family":"Carbajal Zegarra","sequence":"additional","affiliation":[{"name":"Laboratory of Regenerative Medicine, Universidad Nacional Jorge Basadre Grohmann, Tacna 23003, Peru"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0293-1138","authenticated-orcid":false,"given":"Claudio Willbert","family":"Ram\u00edrez Atencio","sequence":"additional","affiliation":[{"name":"Laboratory of Regenerative Medicine, Universidad Nacional Jorge Basadre Grohmann, Tacna 23003, Peru"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1001\/jama.296.14.1731","article-title":"Translation of research evidence from animals to humans","volume":"296","author":"Hackam","year":"2006","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/j.jhep.2020.04.011","article-title":"Animal models for liver disease\u2014A practical approach for translational research","volume":"73","author":"Nevzorova","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1186\/s12967-018-1678-1","article-title":"Is it possible to overcome issues of external validity in preclinical animal research? Why most animal models are bound to fail","volume":"16","author":"Pound","year":"2018","journal-title":"J. Transl. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"104093","DOI":"10.1016\/j.etap.2023.104093","article-title":"Molecular mechanisms in thioacetamide-induced acute and chronic liver injury models","volume":"99","author":"Ezhilarasan","year":"2023","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1177\/0023677215573040","article-title":"Standard operating procedures in experimental liver research: Thioacetamide model in mice and rats","volume":"49","author":"Wallace","year":"2015","journal-title":"Lab. Anim."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.mam.2018.09.002","article-title":"Liver fibrosis: Pathophysiology, pathogenetic targets and clinical issues","volume":"65","author":"Parola","year":"2019","journal-title":"Mol. Aspects Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/2193-1801-2-57","article-title":"Biochemical and histopathological study in rats intoxicated with carbon tetrachloride and treated with camel milk","volume":"2","author":"Althnaian","year":"2013","journal-title":"SpringerPlus"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"111732","DOI":"10.1016\/j.biopha.2021.111732","article-title":"Effects of nerol on paracetamol-induced liver damage in Wistar albino rats","volume":"140","author":"Islam","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e50651","DOI":"10.7554\/eLife.50651","article-title":"The Norway rat, from an obnoxious pest to a laboratory pet","volume":"9","author":"Pisula","year":"2020","journal-title":"eLife"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1016\/S0168-8278(02)00011-9","article-title":"Reproducible production of thioacetamide-induced macronodular cirrhosis in the rat with no mortality","volume":"36","author":"Li","year":"2002","journal-title":"J. Hepatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"S38","DOI":"10.1016\/S0168-8278(02)00429-4","article-title":"Liver fibrosis\u2014From bench to bedside","volume":"38","author":"Friedman","year":"2003","journal-title":"J. Hepatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1172\/JCI24282","article-title":"Liver fibrosis","volume":"115","author":"Bataller","year":"2005","journal-title":"J. Clin. Investig."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3507","DOI":"10.1073\/pnas.1222878110","article-title":"Genomic responses in mouse models poorly mimic human inflammatory diseases","volume":"110","author":"Seok","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"van der Worp, H.B., Howells, D.W., Sena, E.S., Porritt, M.J., Rewell, S., O\u2019Collins, V., and Macleod, M.R. (2010). Can animal models of disease reliably inform human studies?. PLoS Med., 7.","DOI":"10.1371\/journal.pmed.1000245"},{"key":"ref_15","unstructured":"National Research Council (2011). Guide for the Care and Use of Laboratory Animals, National Academies Press. [8th ed.]."},{"key":"ref_16","unstructured":"Council for International Organizations of Medical Sciences (CIOMS), and International Council for Laboratory Animal Science (ICLAS) (2012). International Guiding Principles for Biomedical Research Involving Animals, CIOMS."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/j.taap.2013.09.023","article-title":"Plasma biomarkers of liver injury and inflammation demonstrate a lack of apoptosis during obstructive cholestasis in mice","volume":"273","author":"Woolbright","year":"2013","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Zhao, Y., Liu, X., Ding, C., Gu, Y., and Liu, W. (2021). Dihydromyricetin reverses thioacetamide-induced liver fibrosis through inhibiting NF-\u03baB-mediated inflammation and TGF-\u03b21-regulated PI3K\/Akt signaling pathway. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.783886"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1093\/toxsci\/65.2.166","article-title":"Mechanisms of hepatotoxicity","volume":"65","author":"Jaeschke","year":"2002","journal-title":"Toxicol. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1080\/713611034","article-title":"Hepatotoxicity and mechanism of action of haloalkanes: Carbon tetrachloride as a toxicological model","volume":"33","author":"Weber","year":"2003","journal-title":"Crit. Rev. Toxicol."}],"container-title":["Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-9721\/14\/4\/142\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T04:13:55Z","timestamp":1776140035000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-9721\/14\/4\/142"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,11]]},"references-count":20,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["diseases14040142"],"URL":"https:\/\/doi.org\/10.3390\/diseases14040142","relation":{},"ISSN":["2079-9721"],"issn-type":[{"value":"2079-9721","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,11]]}}}