{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T22:13:58Z","timestamp":1787004838727,"version":"build-2736575974"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":4595,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2003,2]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Two major risk factors for the development of porphyria cutanea tarda (PCT) are alcohol consumption and homozygosity for the C282Y mutation in the hereditary hemochromatosis gene (\n                      <jats:italic toggle=\"yes\">HFE<\/jats:italic>\n                      ). To develop an animal model,\n                      <jats:italic toggle=\"yes\">Hfe<\/jats:italic>\n                      knockout mice were treated continuously with 10% ethanol in drinking water. By 4 months, uroporphyrin (URO) was detected in the urine. At 6 to 7 months, hepatic URO was increased and hepatic uroporphyrinogen decarboxylase (UROD) activity was decreased. Untreated\n                      <jats:italic toggle=\"yes\">Hfe(\u2212\/\u2212)<\/jats:italic>\n                      mice or wild-type mice treated with or without ethanol did not show any of these biochemical changes. Treatment with ethanol increased hepatic nonheme iron and hepatic 5-aminolevulinate synthase activity in\n                      <jats:italic toggle=\"yes\">Hfe(\u2212\/\u2212)<\/jats:italic>\n                      but not wild-type mice. The increases in nonheme iron in\n                      <jats:italic toggle=\"yes\">Hfe(\u2212\/\u2212)<\/jats:italic>\n                      mice were associated with diffuse increases in iron staining of parenchymal cells but without evidence of significant liver injury. In conclusion, the results of this study suggest that the uroporphyrinogenic effect of ethanol is mediated by its effects on hepatic iron metabolism. Ethanol-treated\n                      <jats:italic toggle=\"yes\">Hfe<\/jats:italic>\n                      (\u2212\/\u2212) mice seem to be an excellent model for studies of alcohol-mediated PCT.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1053\/jhep.2003.50034","type":"journal-article","created":{"date-parts":[[2003,2,4]],"date-time":"2003-02-04T21:43:33Z","timestamp":1044395013000},"page":"351-358","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":14,"title":["Uroporphyria caused by ethanol in Hfe (\u2212\/\u2212) mice as a model for porphyria cutanea tarda"],"prefix":"10.1097","volume":"37","author":[{"given":"Peter R.","family":"Sinclair","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Gorman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi W.","family":"Trask","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William J.","family":"Bement","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana G.","family":"Szakacs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George H.","family":"Elder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominic","family":"Balestra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline F.","family":"Sinclair","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glenn S.","family":"Gerhard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"10.1053\/jhep.2003.50034-BIB1","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1055\/s-2007-1007142","volume":"18","author":"Elder","year":"1998","journal-title":"Semin Liver Dis"},{"key":"10.1053\/jhep.2003.50034-BIB2","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1002\/hep.510270142","volume":"27","author":"Elder","year":"1998","journal-title":"Hepatology"},{"key":"10.1053\/jhep.2003.50034-BIB3","first-page":"62","volume-title":"The Porphyrin Handbook II","volume":"14","author":"Elder","year":"2003","unstructured":"Porphyria cutanea tarda and related disorders. 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