Studies on the role of iron in the alterations observed in hexachlorobenzene-induced porphyria.
This study was designed to determine whether iron contents are altered in hexachlorobenzene (HCB)-induced porphyria, and whether there is any relation between these alterations and the effects of the drug on several enzymes of the haem pathway. To this end, the effect of HCB administration on total, non-haem and haem iron levels was studied. Further, the effects of the addition of: both heated and non-heated HCB-porphyric liver preparations, iron as sulfate, ferritin and haemin and alpha alpha'-bipyridyl and 8-hydroxyquinoline were studied on the following enzymes: delta-aminolaevulinic acid synthase, delta-aminolaevulinic acid dehydratase, porphobilinogenase and porphyrinogen carboxy-lyase. Total and non-haem iron levels increased significantly as a result of HCB intoxication, but there was a non-significant decrease in haem iron content. The increased iron levels did not appear to be directly involved in the increased activities of delta-aminolaevulinic acid synthase and delta-aminolaevulinic acid dehydratase observed in HCB-induced porphyria, since it was not possible to detect any activation in heating and crossed assays nor by the addition of inorganic iron, protein-iron or haemin. Results from heating and crossed assays suggested the existence of an activator for porphobilinogenase and an inhibitor for porphyrinogen carboxy-lyase, while results obtained with chelating agents suggested that iron could partly account for the activation of porphobilinogenase. Iron was not directly involved with the decreased activity of porphyrinogen carboxy-lyase, since neither iron chelators nor different types of iron produced physiologically significant effects.
D000818:Animals; D002262:Carboxy-Lyases / Q000037:antagonists & inhibitors; D002614:Chelating Agents / Q000494:pharmacology; D002722:Chlorobenzenes / Q000633:toxicity*; D005260:Female; D006418:Heme / Q000378:metabolism; D006581:Hexachlorobenzene / Q000633:toxicity*; D007501:Iron / Q000032:analysis / Q000502:physiology*; D011164:Porphyrias / Q000139:chemically induced* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D002614:Chelating Agents; D002722:Chlorobenzenes; D006418:Heme; D006581:Hexachlorobenzene; D007501:Iron; D002262:Carboxy-Lyases; C022430:porphyrinogen carboxy-lyase