PHOTODEGRADATION AND PHOTOTOXICITY STUDIES OF FUROSEMIDE - INVOLVEMENT OF SINGLET OXYGEN IN THE PHOTOINDUCED HEMOLYSIS AND LIPID-PEROXIDATION

The phototoxic diuretic drug furosemide (1), a minosulfonyl)-4-chloro- 2-[(2-furanylmethy])-amino] benzoic acid is photolabile under aerobic and anaerobic conditions. Irradiation of a methanol solution of 1 unde r oxygen produces photoproducts 2, 3, 4 and singlet oxygen, while unde r arson the photoproducts 2 and 4 were isolated. A peroxidic unstable photoproduct was detected during the photolysis under oxygen atmospher e. The formation of singlet oxygen by photolysis of 1 was evidenced by trapping with 2,5-dimethylfuran (GC-mass), furfuryl alcohol and 1,3-c yclohexadiene-1,4-diethanoate (HPLC) as O-1(2) scavengers and by the h istidine test. Furosemide was screened in vitro at different concentra tions for UV-Vis-induced phototoxic effects in a photohemolysis test, in the presence and absence of different radical scavengers, singlet o xygen and hydroxyl radical quenchers. However, furosemide photosensiti zed the peroxidation of linoleic acid, as monitored by the UV-detectio n of dienic hydroperoxides and it also photosensitized the oxidation o f histidine. The photodegradation was catalyzed in the presence of hum an serum albumin. Studies on peripheral blood mononuclear and polymorp honuclear cells (lymphocytes and neutrophils) demonstrated no phototox icity on these cell lines. (C) 1998 Elsevier Science S.A. All rights r eserved.