Porphyrin Metabolism in Experimental Hepatic Siderosis in the Rat

Abstract

S ummary . The combination of iron overload and hexachlorobenzene (HCB) feeding in rats produces an ‘experimental symptomatic porphyria’. Studies of hepatic haem biosynthesis in this model showed a decrease in total liver haem and cytochromes P450 and b 5 , together with decreased incorporation of 14 C‐succinate into liver haem and an absence of uroporphyrinogen decarboxylase activity. A marked alteration was found in the redox state of the liver cell cytoplasm both in siderotic and non‐siderotic animals after HCB feeding; the ratio NAD: NADH was increased more than two‐fold. These findings suggest that the primary effect of HCB with regard to liver haem biosynthesis may be this change in the redox state, possibly leading to decreased ability to maintain porphyrinogens in the reduced form and that the additional effect of iron overload is mediated by impairment of uroporphyrinogen decarboxylase activity and an increased rate of degradation of microsomal drug detoxifying cytochromes. It is probable that in human symptomatic porphyria a number of factors are similarly responsible for the excessive production and excretion of porphyrins.