Altered liver parameters in a genetic mouse model of porphyria cutanea tarda and possible involvement of ABC transporters in the disease

The project sought to examine the changes in the liver associated with porphyria and whether ATP binding cassette (ABC) transporters in the hepatocyte might in some manner be connected with the disruption of porphyrin homeostasis. The animal model of porphyria selected for the study was a genetic mouse model of porphyria cutanea tarda (PCT) that spontaneously develops the disorder with maturity. This model affords the opportunity to comprehensively evaluate liver changes without the administration of any exogenous compounds, which in other animal models are used to precipitate PCT. Many changes in hepatic parameters were present in the porphyric mouse model. Total liver heme concentration was increased, select cytochrome P450 activities were decreased while others were unchanged, UDP-glucuronosyltransferase activity was unchanged while glutathione S-transferase activity was elevated. Because of their broad and overlapping substrate selectivities, changes in specific transporters are most easily investigated through changes in mRNA expression.