{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T19:50:20Z","timestamp":1786737020111,"version":"build-2736575974"},"reference-count":29,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":2831,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2007,12]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>\n                                 <jats:bold>Porphyria cutanea tarda is a liver disease characterized by elevated hepatic iron and excessive production of uroporphyrin (URO). Phlebotomy is an effective treatment that probably acts by reducing hepatic iron. Here we used<\/jats:bold>\n                                 <jats:bold>\n                                    Hfe\n                                 <\/jats:bold>\n                                 <jats:bold>(\u2212\/\u2212) mice to compare the effects on hepatic URO accumulation of two different methods of hepatic iron depletion: iron chelation using deferiprone (L1) versus iron-deficient diets.<\/jats:bold>\n                                 <jats:bold>\n                                    Hfe\n                                 <\/jats:bold>\n                                 <jats:bold>(\u2212\/\u2212) mice in a 129S6\/SvEvTac background were fed 5-aminolevulinic acid (ALA), which results in hepatic URO accumulation, and increasing doses of L1 in the drinking water. Hepatic URO accumulation was completely prevented at low L1 doses, which partially depleted hepatic nonheme iron. By histological assessment, the decrease in hepatic URO accumulation was associated with greater depletion of iron from hepatocytes than from Kupffer cells. The L1 treatment had no effect on levels of hepatic cytochrome P4501A2 (CYP1A2). L1 also effectively decreased hepatic URO accumulation in C57BL\/6<\/jats:bold>\n                                 <jats:bold>\n                                    Hfe\n                                 <\/jats:bold>\n                                 <jats:bold>(\u2212\/\u2212) mice treated with ALA and a CYP1A2 inducer. ALA-treated mice maintained on defined iron-deficient diets, rather than chow diets, did not develop uroporphyria, even when the animals were iron-supplemented either directly in the diet or by iron dextran injection.<\/jats:bold>\n                                 <jats:bold>\n                                    Conclusion:\n                                 <\/jats:bold>\n                                 <jats:bold>The results suggest that dietary factors other than iron are involved in the development of uroporphyria and that a modest depletion of hepatocyte iron by L1 is sufficient to prevent URO accumulation. (Hepatology 2007.)<\/jats:bold>\n                              <\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.21903","type":"journal-article","created":{"date-parts":[[2007,9,13]],"date-time":"2007-09-13T19:16:50Z","timestamp":1189711010000},"page":"1927-1834","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":13,"title":["Effect of an oral iron chelator or iron-deficient diets on uroporphyria in a murine model of porphyria cutanea tarda"],"prefix":"10.1097","volume":"46","author":[{"given":"Nadia","family":"Gorman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Zaharia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi S.","family":"Trask","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana G.","family":"Szakacs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas J.","family":"Jacobs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith M.","family":"Jacobs","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":"Peter R.","family":"Sinclair","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R2-31-20241201","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/j.bbamcr.2006.05.005","article-title":"Biosynthesis of heme in mammals.","volume":"1763","author":"Ajioka","year":"2006","journal-title":"Biochim Biophys Acta"},{"key":"R3-31-20241201","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1023\/A:1013746828074","article-title":"Porphyria cutanea tarda: multiplicity of risk factors including HFE mutations, hepatitis C, and inherited uroporphyrinogen decarboxylase deficiency.","volume":"47","author":"Egger","year":"2002","journal-title":"Dig Dis Sci"},{"key":"R4-31-20241201","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1046\/j.1523-1747.2000.00148.x","article-title":"Coinheritance of mutations in the uroporphyrinogen decarboxylase and hemochromatosis genes accelerates the onset of porphyria cutanea tarda.","volume":"115","author":"Brady","year":"2000","journal-title":"J Invest Dermatol"},{"key":"R5-31-20241201","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s004280100401","article-title":"C282Y and H63D mutation of the hemochromatosis gene in German porphyria cutanea tarda patients.","volume":"439","author":"Tannapfel","year":"2001","journal-title":"Virchows Arch"},{"key":"R6-31-20241201","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1042\/bj2580247","article-title":"Oxidation of uroporphyrinogen by methylcholanthreneinduced cytochrome P450. 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