Back to Search
Start Over
Uroporphyria caused by ethanol in Hfe(-/-) mice as a model for porphyria cutanea tarda.
- Source :
-
Hepatology (Baltimore, Md.) [Hepatology] 2003 Feb; Vol. 37 (2), pp. 351-8. - Publication Year :
- 2003
-
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.
- Subjects :
- 5-Aminolevulinate Synthetase metabolism
Animals
Cytochrome P-450 CYP1A2 metabolism
Disease Models, Animal
Hemochromatosis Protein
Histocompatibility Antigens Class I genetics
Iron metabolism
Liver drug effects
Liver metabolism
Liver pathology
Membrane Proteins genetics
Mice
Mice, Knockout genetics
Tissue Distribution
Ethanol pharmacology
Membrane Proteins deficiency
Porphyria Cutanea Tarda chemically induced
Porphyria Cutanea Tarda metabolism
Uroporphyrins urine
Subjects
Details
- Language :
- English
- ISSN :
- 0270-9139
- Volume :
- 37
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Hepatology (Baltimore, Md.)
- Publication Type :
- Academic Journal
- Accession number :
- 12540785
- Full Text :
- https://doi.org/10.1053/jhep.2003.50034