The role of iron in the hexachlorobenzene induced porphyria. I. Studies on different types of iron and its relation with porphyrinogen carboxy-lyase decrease.

Studies were carried out to elucidate if in the hexachlorobenzene (HCB) porphyria, total, nonhaem and haem iron contents in liver are altered and if any relation exists between these alterations and the hepatic porphyrinogen carboxy-lyase (PCL) decrease in rats treated with the drug. It was observed that in porphyric livers total and non-haem iron levels increased significantly as a consequence of HCB intoxication while this treatment produced a non significant decrease in the haem iron content. Enzymic preparations of porphyric livers filtered through Sephadex G-25 columns which separate the free iron and that has a content of iron-protein greater than those in normals, exhibited a strong inhibition of PCL. Chelating agents, alpha' alpha' bipyridyl and 8-hydroxyquinoline do not revert such inhibition. The effect in vitro of ferritin, haemin and inorganic iron at different concentrations on normal PCL activity was also assayed. So, it could be observed that inorganic iron and haemin produce slight inhibition of PCL when added in concentrations higher than those corresponding to a porphyric liver (0.08 mM and 10(-6) M, respectively, as mean in the incubation media). So, they have not physiological significance. Ferritin does not modify the decarboxylation process. From these results it arises that iron does not play a direct role in the decrease of PCL activity in the experimental porphyria by HCB, not being the inhibitor made evident by heating assays. Iron could perhaps stimulate the metabolization of HCB, giving rise to active metabolite.