Afloqualone phototoxicity--photosensitized lipid peroxidative potency and its biological significance.
Photosensitivity due to afloqualone (AQ), a muscle relaxant acting on the central nervous system, has tended to increase with increasing clinical use of this drug by orthopedists. The initial step leading to drug photosensitivity is a photochemical reaction between photo excited phototoxic compounds (drugs) or their metabolites and target molecules in skin. The present study was an attempt to determine whether unsaturated lipids are one of the target molecules of AQ-photosensitivity. Squalene, an unsatulated model lipid, was subjected to UVA irradiation in the presence of AQ and production of squalene hydroperoxides was confirmed. AQ-photosensitized peroxidation of squalene was repressed in the presence of 2.5-dimethylfuran, a singlet oxygen acceptor. Production of singlet oxygen by UVA irradiation of AQ was also observed in aqueous solution. These findings suggested participation of singlet oxygen in the AQ photosensitized peroxidation of squalene. Although photohemolysis was not observed by UVA irradiation in the presence of AQ, We propose that lipids can be a target molecule of AQ-phototoxicity, and lipid peroxidation might be one of the important factors responsible for induction of the AQ phototoxic reaction.
Hayakawa
K
K
Department of Dermatology, School of Medicine, Tokai University, Kanagawa, Japan.
Matsuo
I
I
D006461:Hemolysis / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects / Q000528:radiation effects*; D009125:Muscle Relaxants, Central / Q000528:radiation effects / Q000633:toxicity; D010787:Photosensitivity Disorders / Q000209:etiology*; D011799:Quinazolines / Q000528:radiation effects* / Q000633:toxicity; D014466:Ultraviolet Rays
D009125:Muscle Relaxants, Central; D011799:Quinazolines; C033541:afloqualone