title: Inhibition of plasma lipid oxidation induced by peroxyl radicals, peroxynitrite, hypochlorite, 15-lipoxygenase, and singlet oxygen by clinical drugs.
abstract: With increasing evidence showing the involvement of oxidative stress in the pathogenesis of various diseases, the effects of clinical drugs possessing antioxidant functions have received much attention. The unregulated oxidative modification of biological molecules leading to diseases is mediated by multiple oxidants including free radicals, peroxynitrite, hypochlorite, lipoxygenase, and singlet oxygen. The capacity of antioxidants to scavenge or quench oxidants depends on the nature of oxidants. In the present study, the antioxidant effects of several clinical drugs against plasma lipid oxidation induced by the aforementioned five kinds of oxidants were investigated from the production of lipid hydroperoxides, which have been implicated in the pathogenesis of various diseases. Troglitazone acted as a potent peroxyl radical scavenger, whereas probucol and edaravone showed only moderate reactivity and carvedilol, pentoxifylline, and ebselen did not act as radical scavenger. Probucol and edaravone suppressed plasma oxidation mediated by peroxynitrite and hypochlorite. Troglitazone and edaravone inhibited 15-lipoxygenase mediated plasma lipid oxidation, the IC50being 20 and 34μM respectively. None of the drugs used in this study suppressed plasma lipid oxidation by singlet oxygen. This study shows that the antioxidant effects of drugs depend on the nature of oxidants and that antioxidants against multiple oxidants are required to cope with oxidative stress in vivo.
authors: Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan; Department of Gastrointestinal Immunology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors: Mayuko
authors: M
authors: Morita
authors: Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors: Yuji
authors: Y
authors: Naito
authors: Department of Gastrointestinal Immunology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors: Toshikazu
authors: T
authors: Yoshikawa
authors: Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan; National Institute of Advanced Industrial Science & Technology, Health Research Institute, Takamatsu 761-0395, Japan. Electronic address: etsuo-niki@aist.go.jp.
authors: Etsuo
authors: E
authors: Niki
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D000983:Antipyrine / Q000031:analogs & derivatives / Q000494:pharmacology; D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism*; D000077553:Edaravone; D005609:Free Radicals / Q000378:metabolism; D006997:Hypochlorous Acid / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects*; D008055:Lipids / Q000097:blood; D051379:Mice; D016877:Oxidants / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects*; D010545:Peroxides / Q000378:metabolism; D030421:Peroxynitrous Acid / Q000378:metabolism; D010949:Plasma / Q000187:drug effects* / Q000378:metabolism; D011341:Probucol / Q000494:pharmacology; D026082:Singlet Oxygen / Q000378:metabolism
chemical_list: D000975:Antioxidants; D005609:Free Radicals; D008055:Lipids; D016877:Oxidants; D010545:Peroxides; D030421:Peroxynitrous Acid; D026082:Singlet Oxygen; C049375:perhydroxyl radical; D006997:Hypochlorous Acid; D001093:Arachidonate 15-Lipoxygenase; D011341:Probucol; D000077553:Edaravone; D000983:Antipyrine
keywords: Antioxidant drug; Free radical; Hypochlorite; Lipid oxidation; Lipoxygenase; Peroxynitrite; Singlet oxygen