PRO- AND ANTIOXIDANT FACTORS IN ACUTE INTERMITTENT PORPHYRIA

Rocchi E, Ventura P, Ronzoni A, Rosa MC, Gozzi C, Casalgrandi G

 

Department of Medicine and Medical Specialities, Post Critical Care Unit and Medicine II Unit, University of Modena and Reggio Emilia, Modena, Italy

 

 

Proven the crucial role of iron and porphyrins in the oxidative cellular damage in chronic porphyrias,  we have undertaken an extensive study in families with acute porphyrias in order to evaluate the possible role of similar oxidative damage even in these diseases, whose natural history is often complicated by neoplastic evolution (hepatocellular carcinoma), as well. Four unrelated patients affected by Acute Intermittent Porphyria (AIP) were studied together with 37 members from correspondent different families. All subjects have been assessed for: serum δ-aminolevulinic acid and porphobilinogen; urinary, erythrocyte and fecal porphyrins;  porphobilinogen-deaminase enzymatic activity; iron status (plasma iron, transferrin and ferritin); serum different antioxidants (ascorbic acid, retinol, tocopherol, α- and β-carotene) and urinary and plasma metabolites of nitrous oxide. No significant increase in plasma markers of oxidative damage was observed in PAI patients. No significant correlation between porphyrin precursors accumulation and decrease in the vitamin antioxidant potential was observed; when present, oxidative damage markers resulted significantly related to spontaneous or iatrogenic iron accumulation. Family studies in AIP must also include evaluation of iron stores in order to prevent a further oxidative damage and probably a neoplastic evolution of the disease. The  mechanism underlying the occurrence of neoplastic evolution in PAI in absence of iron accumulation seems however to depend on pathophysiological mechanisms different from those involved in chronic porphyrias (and probably not involving free radicals generation).