Lipid peroxidation induced by phenylbutazone radicals.
Lipid peroxidation was investigated to evaluate the deleterious effect on tissues by phenylbutazone (PB). PB induced lipid peroxidation of microsomes in the presence of horseradish peroxidase and hydrogen peroxide (HRP-H2O2). The lipid peroxidation was completely inhibited by catalase but not by superoxide dismutase. Mannitol and dimethylsulfoxide had no effect. These results indicated no paticipation of superoxide and hydroxyl radical in the lipid peroxidation. Reduced glutathione (GSH) efficiently inhibited the lipid peroxidation. PB radicals emitted electron spin resonance (ESR) signals during the reaction of PB with HRP-H2O2. Microsomes and arachidonic acid strongly diminished the ESR signals, indicating that PB radicals directly react with unsaturated lipids of microsomes to cause thiobarbituric acid reactive substances. GSH sharply diminished the ESR signals of PB radicals, suggesting that GSH scavenges PB radicals to inhibit lipid peroxidation. Also, 2-methyl-2-nitrosopropan strongly inhibited lipid peroxidation. R-Phycoerythrin, a peroxyl radical detector substance, was decomposed by PB with HRP-H2O2. These results suggest that lipid peroxidation of microsomes is induced by PB radicals or peroxyl radicals, or both.
Miura
Toshiaki
T
Hokkaido College of Pharmacy, Otaru, Japan. miurat@hokuyakudai.ac.jp
Muraoka
Sanae
S
Fujimoto
Yukio
Y
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002374:Catalase / Q000494:pharmacology; D004578:Electron Spin Resonance Spectroscopy; D016166:Free Radical Scavengers / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D006735:Horseradish Peroxidase / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008353:Mannitol / Q000494:pharmacology; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction; D010545:Peroxides / Q000378:metabolism; D010653:Phenylbutazone / Q000494:pharmacology*; D010799:Phycoerythrin / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016166:Free Radical Scavengers; D010545:Peroxides; D010799:Phycoerythrin; C049375:perhydroxyl radical; D008353:Mannitol; D006861:Hydrogen Peroxide; D006735:Horseradish Peroxidase; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione; D010653:Phenylbutazone