{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T15:13:25Z","timestamp":1778080405158,"version":"3.51.4"},"reference-count":46,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T00:00:00Z","timestamp":1778025600000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100012021","name":"Iran University of Medical Sciences","doi-asserted-by":"publisher","award":["32608"],"award-info":[{"award-number":["32608"]}],"id":[{"id":"10.13039\/100012021","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Acrylamide (ACR) is formed as a byproduct during high\u2010temperature processing of carbohydrate\u2010rich, low\u2010protein foods and represents a widespread dietary contaminant. Given the extensive daily human exposure, its hepatotoxic potential is a growing concern. Therefore, this study aimed to evaluate the protective effects of crocin and pentoxifylline (PTX), administered individually or in combination, against ACR\u2010induced hepatotoxicity in an animal model. Thirty male NMRI mice were randomly assigned to five groups (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20096): normal, ACR, ACR\u2009+\u2009crocin, ACR\u2009+\u2009PTX, and ACR\u2009+\u2009crocin\u2009+\u2009PTX. Crocin (50\u2009mg\/kg) and PTX (50\u2009mg\/kg) were administered orally for 2 weeks. Hepatotoxicity was induced by a single intraperitoneal injection of ACR (10\u2009\u03bcg\/kg), and animals were euthanized 24\u2009h later. Serum samples were collected for the assessment of liver function, oxidative stress, antioxidant defense, and inflammatory markers, while liver tissues were subjected to histopathological and molecular analyses. Crocin significantly reduced IL\u20106 (~19%) and increased CAT activity (~14%), whereas PTX decreased TNF\u2010\u03b1 levels and elevated GSH (~31.7%). In contrast, the combined crocin\u2009+\u2009PTX treatment exerted more pronounced protective effects, significantly reducing ALT and AST levels, lowering TNF\u2010\u03b1 (~31.25%) and IL\u20106 (~20.7%), and attenuating oxidative stress through reductions in MDA (~19.75%) and TOS (~17.5%), accompanied by a marked increase in TAC (~63.2%). This combination also enhanced CAT activity (~25%) and GSH levels (~44.4%), although SOD activity remained unchanged. At the gene expression level, none of the interventions fully restored Nrf2 or FOXO3a expression; however, PTX significantly upregulated FOXO3a expression, resulting in a ~26\u2010fold increase compared to the ACR group, although levels remained markedly lower than those of the normal group. Histopathological evaluation revealed reduced hepatic damage in the treatment groups. Overall, these findings suggest that while crocin and PTX individually confer limited protection, their combined administration exerts a significant synergistic hepatoprotective effect against ACR\u2010induced toxicity.\n                  <\/jats:p>","DOI":"10.1002\/jbt.70810","type":"journal-article","created":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T14:36:31Z","timestamp":1778078191000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Protective Effects of Crocin and Pentoxifylline, Alone and in Combination, in Alleviating Acrylamide\u2010Induced Hepatic Injury in NMRI Mice"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1819-853X","authenticated-orcid":false,"given":"Yaser","family":"Mohammadi","sequence":"first","affiliation":[{"name":"Student Research Committee Iran University of Medical Sciences Tehran Iran"},{"name":"Department of Biochemistry, School of Medicine Iran University of Medical Sciences Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9913-986X","authenticated-orcid":false,"given":"Reyhaneh","family":"Taebi","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, School of Medicine Shahid Beheshti University of Medical Sciences Tehran Iran"},{"name":"Student Research Committee, School of Medicine Shahid Beheshti University of Medical Sciences Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6823-8638","authenticated-orcid":false,"given":"Elham","family":"Bahreini","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Medicine Iran University of Medical Sciences Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1517-7162","authenticated-orcid":false,"given":"Mohammad","family":"Babaei","sequence":"additional","affiliation":[{"name":"Department of Basic Sciences, Faculty of Veterinary Medicine Bu\u2010Ali Sina University Hamedan Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asieh","family":"Hosseini","sequence":"additional","affiliation":[{"name":"Razi Drug Research Center Iran University of Medical Sciences Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,5,6]]},"reference":[{"issue":"5","key":"e_1_2_11_2_1","first-page":"233","article-title":"Drug\u2010Induced Hepatotoxicity: A Review","volume":"2","author":"Pandit A.","year":"2012","journal-title":"Journal of Applied Pharmaceutical Science"},{"issue":"4","key":"e_1_2_11_3_1","first-page":"637","article-title":"Worldwide Prevalence, Genotype Distribution and Management of Hepatitis C","volume":"84","author":"Guntipalli P.","year":"2021","journal-title":"Acta Gastroenterologica Belgica"},{"key":"e_1_2_11_4_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s12403-017-0261-y","article-title":"Acrylamide in Environmental Water: A Review on Sources, Exposure, and Public Health Risks","volume":"11","author":"Tepe Y.","year":"2019","journal-title":"Exposure and Health"},{"issue":"9","key":"e_1_2_11_5_1","doi-asserted-by":"crossref","first-page":"2503","DOI":"10.3390\/nu12092503","article-title":"Dietary Acrylamide Intake and the Risk of Liver Cancer: The Japan Public Health Center\u2010Based Prospective Study","volume":"12","author":"Zha L.","year":"2020","journal-title":"Nutrients"},{"issue":"16","key":"e_1_2_11_6_1","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1089\/ars.2022.0055","article-title":"Acrylamide\u2010Induced Hepatotoxicity Through Oxidative Stress: Mechanisms and Interventions","volume":"38","author":"Zhang L.","year":"2023","journal-title":"Antioxidants & Redox Signaling"},{"issue":"12","key":"e_1_2_11_7_1","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1177\/0960327116686818","article-title":"Evidence of Acrylamide\u2010 and Glycidamide\u2010Induced Oxidative Stress and Apoptosis in Leydig and Sertoli Cells","volume":"36","author":"Yilmaz B. 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