THE EFFECT OF PORPHYRINS ON CELLULAR REDOX SYSTEMS - A STUDY ON THE DARK EFFECT OF PORPHYRINS ON PHAGOCYTES

Erythropoietic protoporphyria (EPP) and porphyria cutanea tarda (PCT) are characterized by skin morbidity, induced by pro-inflammatory react ive oxygen species generated by the photosensitizing properties of pro toporphyrin IX and uroporphyrin I. How these porphyrins exert a toxic effect on the liver in the absence of light is poorly understood. We t ested the hypothesis that porphyrins can interference with cellular re dox systems, by studying the dark effects of protoporphyrin (PP), haem atoporphyrin (HP), deuteroporphyrin (DP) and uroporphyrin (UP) on the cellular redox system of phagocytes, and on enzymatic oxyradical gener ating systems. Both in phagocytic cells and enzymatic systems, a dose- dependent inhibition of chemiluminescence was observed by all porphyri ns added. Catalase and SOD-like activity of porphyrins was excluded by oxygraph and ferricytochrome c reduction. However, ferrocytochrome c oxidation was inhibited by porphyrins indicating ferrireductase-like a ctivity. In a Fenton type reaction between H2O2 and PP, we could demon strate the generation of .OH, or an electronically excited porphyrin s pecies. No influence on phagocyte chemotaxis, phagocytosis and killing -capacity was observed. We conclude that porphyrins do interfere with (cellular) redox systems and can both inhibit and enhance oxygen free radical generation, dependent on the type of redox reaction. Porphyrin s can thus affect cellular metabolism. Since H(2)0(2) and PP both read ily dissolve in biological membranes, their interaction in the presenc e of transition metals may contribute to the toxic dark effects of por phyrins as observed in patients with EPP and PCT.