Chemische, biologische und immunologische Untersuchungen von Photooxidationsprodukten der Furocumarine (Psoralene). Entwicklung einer neuen Methode fuer die Psoralentherapie Schlussbericht

Furocoumarins (FC) combined with UV-A irradiation are used for treatment of skin diseases (PUVA-therapy). It was accepted that the molecular basis of therapeutic effects was the oxygen-independent cyclophotoaddition of FCs to DNA. Potapenko et al. reported (1994) that mixture of products of FC photooxidation (POP) possessed antileukemic, and immunomodulative properties, thus, POP mimics main effects of PUVA-therapy. However, the chemical structure of POP were not elucidated. Adam et al. (1993) assessed the chemical structure of photooxidation products of several FCs (imperatorin (I), alloimperatorin (II), trimethylpsoralen (III)). Those products were shown to be able of oxidative damage of DNA in cells. The aim of the project was to study immunomodulative and membranotoxic effects of products of photooxidation of I and II to assess their potential application for therapy. Isolation and characterization of photoproducts were done by HPLC and column chromatography, and by MS, IR and NMR spectroscopy. Biological and immunological investigations were conducted using dark and photosensitized hemolysis of erythrocytes, and the delayed type hypersensitivity reaction (DTH) in mice. We found that hydroperoxides of I and II induced hemolysis and transferrable suppression of DTH. The latter was independent of the mode of application of hydroperoxides (intravenous injection or per os administration) and was due to induction of DTH supressor cells in mice spleen. Membranotoxic effects of FCs I and II are caused by hydroxyl redicals, which are generated from intermediary hydroperoxides. These hydroperoxides also induced hemoglobin crosslinking as well as its conversion into methemoglobin and hemichrom. FC hydroperoxides may serve as potential therapeutic agents for T cell mediated disorders. A novel method of FC therapy, which employs FC photooxidation products, may be developed. This method may be designated as photochemotherapy in the dark, because it need not irradiation of patients' skin or blood. (orig.)SIGLEAvailable from TIB Hannover: DtF QN1(57,16) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Bildung, Wissenschaft, Forschung und Technologie, Bonn (Germany)DEGerman