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 reactive oxygen species generated by the photosensitizing properties of protoporphyrin IX and uroporphyrin I. How these porphyrins exert a toxic effect on the liver in the absence of light is poorly understood. We tested the hypothesis that porphyrins can interference with cellular redox systems, by studying the dark effects of protoporphyrin (PP), haematoporphyrin (HP), deuteroporphyrin (DP) and uroporphyrin (UP) on the cellular redox system of phagocytes, and on enzymatic oxyradical generating systems. Both in phagocytic cells and enzymatic systems, a dose-dependent inhibition of chemiluminescence was observed by all porphyrins 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 activity. In a Fenton type reaction between H2O2 and PP, we could demonstrate the generation of .OH, or an electronically excited porphyrin species. 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. Porphyrins can thus affect cellular metabolism. Since H2O2 and PP both readily dissolve in biological membranes, their interaction in the presence of transition metals may contribute to the toxic dark effects of porphyrins as observed in patients with EPP and PCT.
Koningsberger
J C
JC
Department of Gastroenterology, University Hospital Utrecht, The Netherlands.
Van Asbeck
B S
BS
Van Hattum
J
J
Wiegman
L J
LJ
Van Berge Henegouwen
G P
GP
Marx
J J
JJ
D003574:Cytochrome c Group / Q000378:metabolism; D003624:Darkness; D006801:Humans; D017665:Hydroxyl Radical / Q000378:metabolism; D008163:Luminescent Measurements; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D010084:Oxidation-Reduction; D010586:Phagocytes / Q000187:drug effects* / Q000502:physiology; D011166:Porphyrins / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism
D003574:Cytochrome c Group; D011166:Porphyrins; D013481:Superoxides; D017665:Hydroxyl Radical