Uroporphyria induced by 5-aminolaevulinic acid alone in ahrd SWR mice

摘要: In mice, depression of hepatic uroporphyrinogen decarboxylase (UROD) leading to porphyrin accumulation (uroporphyria) occurs with chlorinated ligands the aryl hydrocarbon (AH) receptor especially after iron overload. However, in absence ligands, itself will eventually cause uroporphyria, but this response is not associated Ahr genotype. These effects are potentiated by administration haem precursor 5-aminolaevulinate (ALA). The aim study was investigate ALA alone. Prolonged 2 mg ALA/mL drinking water SWR mice also led insufficiency (11% control) and uroporphyria 8 weeks, whereas DBA/2 did show reduced enzyme activity. Both strains considered AH nonresponsive analysis gene using restriction fragment length polymorphism consistent SWR, like DBA/2, possessing Ahrd allele. Exposure isolated hepatocytes (150-500 microM) for up 48 hr showed a significant both uroporphyrin coproporphyrin medium, which particularly significantly greater than cells. Basal vivo CYP1A2 activity, measured as microsomal methoxyresorufin dealkylation, (1.3-fold), it unclear whether sufficient explain marked difference sensitivities two strains. Despite being nonresponsive, an initial overload 3 weeks were greatly single dose (100 mg/kg) hexachlorobenzene (a weak ligand). results demonstrate that there genetic independent genotype iron, influences susceptibility ALA-induced uroporphyria. Thus chemicals, can act independently, together, porphyria susceptible individuals.