title: Antioxidative activity of 5,6,7,8-tetrahydrobiopterin and its inhibitory effect on paraquat-induced cell toxicity in cultured rat hepatocytes.
abstract: The in vitro antioxidative activity of 5,6,7,8-tetrahydrobiopterin (BPH4) was measured and the ability of BPH4 to prevent paraquat-induced cell damage was examined in cultured hepatocytes. The scavenging activity of BPH4 against superoxide anion radicals was assayed in two systems, i.e., xanthine/xanthine oxidase (X/XOD) and rat macrophage/phorbol myristate acetate (M psi/PMA) radical-generating systems. BPH4 showed an extremely strong superoxide anion radical-scavenging activity in both assay systems. Biopterin (BP) itself did not show any activity in the X/XOD system, but was effective in the M psi/PMA system. The antioxidative activities of BPH4 against both superoxide anion and hydroxyl radicals were confirmed by spin trapping-ESR spectrometry. BPH4 also protected rat brain homogenate against auto-oxidation. We further examined the effect of BPH4 on paraquat-induced cell toxicity in cultured rat hepatocytes. The paraquat-induced elevation of the release of lactate dehydrogenase (LDH), a marker enzyme for cytotoxicity from cultured hepatocytes was suppressed by BPH4 in a dose-dependent manner. The elevation of lipid peroxides simultaneously induced by paraquat was also inhibited by BPH4 in the same manner. These results suggest that BPH4 might be useful in the treatment of various diseases whose pathogenesis is active oxygen-related.
authors.affiliation: Research Institute for Biosciences, Science University of Tokyo, Chiba, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Kojima
authors.forename: S
authors.initials: S
authors.lastname: Ona
authors.forename: I
authors.initials: I
authors.lastname: Iizuka
authors.forename: T
authors.initials: T
authors.lastname: Arai
authors.forename: H
authors.initials: H
authors.lastname: Mori
authors.forename: K
authors.initials: K
authors.lastname: Kubota
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001708:Biopterins / Q000031:analogs & derivatives* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004578:Electron Spin Resonance Spectroscopy; D016166:Free Radical Scavengers / Q000494:pharmacology; D017665:Hydroxyl Radical / Q000378:metabolism; D008054:Lipid Peroxides / Q000032:analysis / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D008163:Luminescent Measurements; D008264:Macrophages / Q000187:drug effects / Q000502:physiology; D008297:Male; D010269:Paraquat / Q000037:antagonists & inhibitors / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D019820:Xanthine; D014969:Xanthine Oxidase / Q000378:metabolism; D014970:Xanthines / Q000378:metabolism
chemical_list: D000975:Antioxidants; D016166:Free Radical Scavengers; D008054:Lipid Peroxides; D014970:Xanthines; D013481:Superoxides; D019820:Xanthine; D001708:Biopterins; D017665:Hydroxyl Radical; D014969:Xanthine Oxidase; C003402:sapropterin; D013755:Tetradecanoylphorbol Acetate; D010269:Paraquat