title: Chemiluminescence associated with the oxidative metabolism of salicylic acid in rat liver microsomes.
abstract: Rat liver microsomal suspension (1 mg protein per ml) was incubated at 37 degrees C with 5 mM salicylic acid and 0.2 mM NADPH. The amounts of thiobarbituric acid reactive substances (TBARS) and 2,5-dihydroxybenzoic acid (2,5-DHB), an oxidative metabolite of salicylic acid increased with the incubation time. Simultaneously spontaneous chemiluminescence (CL) was found to be generated there. The addition of SKF-525A, an inhibitor of cytochrome P450 (P450), to the reaction mixture inhibited the CL generation together with the inhibition of the oxidative metabolism. The anti-oxidants and singlet oxygen scavengers like N,N-diphenylphenylenediamine (DPPD) and histidine suppressed the CL generation. The addition of 1,4-diazabicyclo [2.2.2] octane (DABCO), a singlet oxygen quencher, to the reaction mixture generating CL enhanced CL transiently and then CL decreased markedly. Thus CL observed here may possibly originate from the singlet oxygen. The CL generation was suggested to be closely related with salicylic acid-induced lipid peroxidation, and to be coupled with the oxidative metabolism mediated by P450 in rat liver microsomes.
authors.affiliation: Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi-cho, Inage-ku, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Doi
authors.forename: Hiromi
authors.initials: H
authors.lastname: Iwasaki
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Masubuchi
authors.forename: Ryuichiro
authors.initials: R
authors.lastname: Nishigaki
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Horie
mesh_terms: D000818:Animals; D001711:Biotransformation; D002927:Cimetidine / Q000494:pharmacology; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007700:Kinetics; D008163:Luminescent Measurements; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D011335:Proadifen / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D020156:Salicylic Acid / Q000493:pharmacokinetics*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D017392:Thiobarbituric Acid Reactive Substances; D009249:NADP; D002927:Cimetidine; D011335:Proadifen; D020156:Salicylic Acid