<title>Mechanism of photobiological effects of psoralens: the involvement of photo-oxidized psoralens as reactive intermediate species in induction of photosensitized hemolysis and skin erythema</title>

Abstract

Psoralens combined with UVA irradiation (320-400 nm) are used for the treatment of skin and autoimmune diseases (PUVA-therapy). In the present paper the involvement of psoralen photooxidation products (POP) into induction of PUVA-erythema was studied. Under low fluence rate (LFR) UVA-irradiation and/or at low psoralen concentrations POP1-products were predominantly formed, which were detected by spin trap method and possessed immunosuppressive activity. Under high fluence rate (HFR) UVA-irradiation and/or at high psoralen concentrations POP2-products were predominantly formed, which could be detected by Fe(II)-induced chemiluminescence and possessed hemolytic activity. Both PUVA-and POP-induced hemolysis of erythrocytes as well as PUVA-erytherna were strongly activated with the increase in UVA-fluence rate. Both LFR and HFR PUVA-hemolysis as well as POPhemolysis were strongly activated by Fe(II)-ions, bivalent cation chelators produced different effects on these processes depending on UVA fluence rate. Ethylenediaminetetraacetate (EDTA), and o-fenanthroline were found to inhibit LFR PUVA-erythema and enhanced HFR PUVAerythema. Similar regulatory effects of EDTA were found for PUVA-and POP-induced hemolysis. EDTA inhibitied LFR PUVA-hemolysis and activated HFR PUVA-and POP-hemolysis that suggests a participation of POP1-products in induction of LFR PUVA-hernolysis and LFR PUVA-erythema and POP2-products in induction of HFR PUVA-hemolysis and HFR PUVA-erythema.