AI Article Synopsis
- Two key risk factors for porphyria cutanea tarda (PCT) are alcohol consumption and having two copies of the C282Y mutation in the hereditary hemochromatosis gene.
- Researchers created an animal model using Hfe knockout mice given 10% ethanol in their water, which showed biochemical changes related to PCT, including increased uroporphyrin in urine and liver after several months.
- The study concludes that ethanol influences liver iron metabolism, making the ethanol-treated Hfe(-/-) mice a suitable model for examining how alcohol contributes to PCT.
Article Abstract
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 (HFE). To develop an animal model, Hfe 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 Hfe(-/-) 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 Hfe(-/-) but not wild-type mice. The increases in nonheme iron in Hfe(-/-) 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 Hfe(-/-) mice seem to be an excellent model for studies of alcohol-mediated PCT.
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| http://dx.doi.org/10.1053/jhep.2003.50034 | DOI Listing |
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