Formation of active oxygen species and lipid peroxidation induced by hypochlorite.
Hypochlorite or its acid, hypochlorous acid, may exert both beneficial and toxic effects in vivo. In order to understand the role and action of hypochlorite, the formation of active oxygen species and its kinetics were studied in the reactions of hypochlorite with peroxides and amino acids. It was found that tert-butyl hydroperoxide and methyl linoleate hydroperoxide reacted with hypochlorite to give peroxyl and/or alkoxyl radicals with little formation of singlet oxygen in contrast to hydrogen peroxide, which gave singlet oxygen exclusively. Amino acids and ascorbate reacted with hypochlorite much faster than peroxides. Free radical-mediated lipid peroxidation of micelles and membranes in aqueous suspensions was induced by hypochlorite, the chain initiation being the decomposition of hydroperoxides by hypochlorite. It was suppressed efficiently by ebselen which reduced hydroperoxides and by alpha-tocopherol, which broke chain propagation, but less effectively by hydrophilic antioxidants present in the aqueous phase. Cysteine suppressed the oxidation, but it was poorer antioxidant than alpha-tocopherol. Ascorbate also exerted moderate antioxidant capacity, but it acted as a synergist with alpha-tocopherol. Taken together, it was suggested that the primary target of hypochlorite must be sulfhydryl and amino groups in proteins and that the lipid peroxidation may proceed as the secondary reaction, which is induced by radicals generated from sulfenyl chlorides and chloramines.
Noguchi
Noriko
N
Research Center for Advanced Science and Technology, University of Tokyo, 4-6-1 Komaba, Meguro, Tokyo, 153-8904, Japan. nonoriko@oxygen.rcast.u-tokyo.ac.jp
Nakada
Akihiro
A
Itoh
Yasuhiro
Y
Watanabe
Akira
A
Niki
Etsuo
E
D000596:Amino Acids / Q000737:chemistry; D000975:Antioxidants / Q000494:pharmacology; D001393:Azoles / Q000494:pharmacology; D006997:Hypochlorous Acid / Q000737:chemistry*; D054833:Isoindoles; D008041:Linoleic Acids / Q000737:chemistry; D015227:Lipid Peroxidation; D008054:Lipid Peroxides / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry; D008956:Models, Chemical; D016566:Organoselenium Compounds / Q000494:pharmacology; D010084:Oxidation-Reduction / Q000187:drug effects; D010713:Phosphatidylcholines / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000737:chemistry
D000596:Amino Acids; D000975:Antioxidants; D001393:Azoles; D054833:Isoindoles; D008041:Linoleic Acids; D008054:Lipid Peroxides; D008081:Liposomes; D016566:Organoselenium Compounds; D010713:Phosphatidylcholines; D017382:Reactive Oxygen Species; C005575:methyl linoleate; C042986:ebselen; D006997:Hypochlorous Acid