Circulating pro- and antioxidant factors in iron and porphyrin metabolism disorders

Background: Porphyria cutanea tarda and haemochromatosis are taken to be sp ontaneous human models of oxidative cellular damage, with an increased risk of fibrosis and cancer evolution. Aim: To define the relative pro-oxidant roles of porphyrin and iron, in the ir different molecular forms, and their effects on antioxidant biological s ystems. Patients: A group of 17 patients with porphyria cutanea tarda and a group o f 14 patients with primary and secondary haemochromatosis, were compared wi th 21 healthy controls. Methods: Plasma retinol, tocopherol, alpha- and beta-carotene, ascorbic aci d, glutathione, malonyldialdehyde and red blood cell free iron were determi ned using high performance liquid chromatography. Results: Only a modest increase in iron stores was demonstrated in the porh pyria cutanea tarda group; in the haemochromatosis patients ferritin levels were almost seven times higher By contrast, there was a sharp and virtuall y identical increase in red blood cell free iron and malonyldialdehyde in b oth the patient groups. A significant reduction was observed in retinol, al pha-, beta-carotene and red blood cell glutathione levels being more marked in porphyria cutanea tarda than in haemochromatosis patients. Conclusions: The study confirms the strong pro-oxidant effects of porphyrin s in vivo, through an induction of the free toxic iron form, even though th e total iron pool is not greatly expanded. The additional free-iron and por phyrin oxidant effects are documented both in red blood cell and plasma in the porphyria cutanea tarda group. It confirmed that aging exerts a negativ e influence in terms of pro- and antioxidant balance in all cases, but part icularly in the haemochromatosis group.