{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T12:45:54Z","timestamp":1789821954857,"version":"4.0.1"},"reference-count":39,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,9,11]],"date-time":"2020-09-11T00:00:00Z","timestamp":1599782400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["20K06415"],"award-info":[{"award-number":["20K06415"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["17K08084"],"award-info":[{"award-number":["17K08084"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP20am0101123"],"award-info":[{"award-number":["JP20am0101123"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Hepatic iron overload is well known as an important risk factor for progression of liver diseases; however, it is unknown whether it can alter the susceptibility to drug-induced hepatotoxicity. Here we investigate the pathological roles of iron overload in two single-dose models of chemically-induced liver injury. Rats were fed a high-iron (Fe) or standard diet (Cont) for four weeks and were then administered with allyl alcohol (AA) or carbon tetrachloride (CCl4). Twenty-four hours after administration mild mononuclear cell infiltration was seen in the periportal\/portal area (Zone 1) in Cont-AA group, whereas extensive hepatocellular necrosis was seen in Fe-AA group. Centrilobular (Zone 3) hepatocellular necrosis was prominent in Cont-CCl4 group, which was attenuated in Fe-CCl4 group. Hepatic lipid peroxidation and hepatocellular DNA damage increased in Fe-AA group compared with Cont-AA group. Hepatic caspase-3 cleavage increased in Cont-CCl4 group, which was suppressed in Fe-CCl4 group. Our results showed that dietary iron overload exacerbates AA-induced Zone-1 liver injury via enhanced oxidative stress while it attenuates CCl4-induced Zone-3 liver injury, partly via the suppression of apoptosis pathway. This study suggested that susceptibility to drugs or chemical compounds can be differentially altered in iron-overloaded livers.<\/jats:p>","DOI":"10.3390\/nu12092784","type":"journal-article","created":{"date-parts":[[2020,9,11]],"date-time":"2020-09-11T09:05:16Z","timestamp":1599815116000},"page":"2784","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Dietary Iron Overload Differentially Modulates Chemically-Induced Liver Injury in Rats"],"prefix":"10.3390","volume":"12","author":[{"given":"Mutsuki","family":"Mori","sequence":"first","affiliation":[{"name":"Laboratory of Veterinary Pathology, Osaka Prefecture University, 1-58 Rinku Orai Kita, Osaka 598-8531, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3236-6050","authenticated-orcid":false,"given":"Takeshi","family":"Izawa","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Pathology, Osaka Prefecture University, 1-58 Rinku Orai Kita, Osaka 598-8531, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yohei","family":"Inai","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Pathology, Osaka Prefecture University, 1-58 Rinku Orai Kita, Osaka 598-8531, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sho","family":"Fujiwara","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Pathology, Osaka Prefecture University, 1-58 Rinku Orai Kita, Osaka 598-8531, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryo","family":"Aikawa","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Pathology, Osaka Prefecture University, 1-58 Rinku Orai Kita, Osaka 598-8531, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuru","family":"Kuwamura","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Pathology, Osaka Prefecture University, 1-58 Rinku Orai Kita, Osaka 598-8531, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jyoji","family":"Yamate","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Pathology, Osaka Prefecture University, 1-58 Rinku Orai Kita, Osaka 598-8531, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"491","DOI":"10.4254\/wjh.v9.i10.491","article-title":"Drug-induced liver injury: Do we know everything?","volume":"9","author":"Alempijevic","year":"2017","journal-title":"World J. 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