Visible light-sensitized oxidation of arachidonic acid in the presence of inperatorin.
To understand the mechanism of the phototoxic effects of inperatorin, a psoralen derivative used as a pigmentation agent, we have investigated the photosensitized oxidation of arachidonic acid (ARA) by irradiation with visible light (> 400 nm) in the presence of inperatorin. HPLC and GC/MS analyses of the products showed the formation of many hydroperoxyeicosatetraenoic acids (HPETEs) including the products of lipoxygenase-catalyzed reactions such as 5- and 15-HPETEs, which are the precursors of chemical mediators such as leukotrienes and lipoxins, during the reaction. Active oxygen scavening agents such as D-mannitol, superoxide dismutase, and beta-carotene inhibited the formation of the oxidation products, indicating that the oxidation reaction was mediated by various active oxygen species. These results suggest that the phototoxic effects of inperatorin could also be induced by visible light and could be explained at least partially in terms of inflammation initiated by the biologically active HPETEs arising from photosensitized oxygenation reactions of ARA with the drug.
D016718:Arachidonic Acid / Q000737:chemistry*; D001894:Borohydrides / Q000737:chemistry; D002338:Carotenoids / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D011564:Furocoumarins / Q000737:chemistry* / Q000633:toxicity; D008401:Gas Chromatography-Mass Spectrometry; D015289:Leukotrienes / Q000737:chemistry; D008027:Light; D008054:Lipid Peroxides / Q000737:chemistry; D008353:Mannitol / Q000494:pharmacology; D010084:Oxidation-Reduction; D010777:Photochemistry; D017319:Photosensitizing Agents / Q000737:chemistry* / Q000633:toxicity; D017382:Reactive Oxygen Species / Q000737:chemistry; D013482:Superoxide Dismutase / Q000494:pharmacology; D019207:beta Carotene
D001894:Borohydrides; D011564:Furocoumarins; D015289:Leukotrienes; D008054:Lipid Peroxides; D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species; C096540:inperatorin; D019207:beta Carotene; D016718:Arachidonic Acid; D002338:Carotenoids; D008353:Mannitol; C025086:15-hydroperoxy-5,8,11,13-eicosatetraenoic acid; C025348:arachidonic acid 5-hydroperoxide; C025364:sodium borohydride; D013482:Superoxide Dismutase