title: Accumulation of uroporphyrin does not provoke further inhibition of liver uroporphyrinogen decarboxylase activity in hexachlorobenzene-induced porphyria.
abstract: The inhibition of uroporphyrinogen decarboxylase (Uro-D) is the basic pathogenetic mechanism in porphyria caused by hexachlorobenzene (HCB). This study aimed to establish whether hepatic accumulation of uroporphyrin in this porphyria could provoke a further decrease of Uro-D activity. Male C57Bl/6 mice were treated for 8 weeks with a diet containing 0.02% HCB. In some of them the deposition of liver porphyrins was additionally increased by intraperitoneal application of delta-aminolaevulinic acid (ALA). Uro-D activity was determined by measuring unconverted substrate uroporphyrinogen after its oxidation to uroporphyrin by reversed-phase high performance liquid chromatography. The value of endogenously formed uroporphyrin was also obtained from the sample by subtraction, using a blank assay. HCB treatment resulted in reduced activity of hepatic Uro-D, but this activity was not significantly less in animals loaded with ALA than in non-loaded mice. Uroporphyrin deposition tended to decrease 6 weeks after withdrawal of HCB, but the activity of Uro-D was still markedly inhibited. There was no evidence that the accumulation of uroporphyrin promoted a supplementary decrease of Uro-D activity in HCB porphyria.
mesh_terms: D000818:Animals; D002262:Carboxy-Lyases / Q000037:antagonists & inhibitors*; D002722:Chlorobenzenes / Q000633:toxicity*; D006581:Hexachlorobenzene / Q000633:toxicity*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011164:Porphyrias / Q000139:chemically induced / Q000378:metabolism*; D011166:Porphyrins / Q000378:metabolism*; D014575:Uroporphyrinogen Decarboxylase / Q000037:antagonists & inhibitors*; D014578:Uroporphyrins / Q000378:metabolism*
chemical_list: D002722:Chlorobenzenes; D011166:Porphyrins; D014578:Uroporphyrins; D006581:Hexachlorobenzene; D002262:Carboxy-Lyases; D014575:Uroporphyrinogen Decarboxylase