The involvement of iron and lipid peroxidation in the pathogenesis of HCB induced porphyria.
Hexachlorobenzene (HCB) induces a porphyria characterized by a diminished activity of the enzyme uroporphyrinogen decarboxylase (URO-D), presumably due to inactivation by reactive metabolites of HCB. We studied the effect of iron on HCB porphyria in female rats, to determine whether the iron dependent process of lipid peroxidation was involved in the pathogenesis of porphyria. We showed that malondialdehyde formation is increased in rat liver tissue of porphyric rats and that high molecular weight proteins due to cross-linking are formed. We also showed that the induction of porphyria by HCB is dependent on the presence of iron. Our findings suggest that lipid peroxidation is involved in the toxicity of HCB and that the aggravating effects of iron on HCB are mediated by lipid peroxidation.
D000818:Animals; D002722:Chlorobenzenes / Q000633:toxicity*; D005260:Female; D006581:Hexachlorobenzene / Q000633:toxicity*; D007501:Iron / Q000502:physiology*; D008054:Lipid Peroxides / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D011164:Porphyrias / Q000139:chemically induced*; D051381:Rats; D011919:Rats, Inbred Strains; D014575:Uroporphyrinogen Decarboxylase / Q000037:antagonists & inhibitors
D002722:Chlorobenzenes; D008054:Lipid Peroxides; D006581:Hexachlorobenzene; D007501:Iron; D014575:Uroporphyrinogen Decarboxylase