Chemiluminescence associated with the oxidative metabolism of salicylic acid in rat liver microsomes

Rat liver microsomal suspension (1 mg protein per ml) was incubated at 37 °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...

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Bibliographic Details
Published in:Chemico-biological interactions 2002-05, Vol.140 (2), p.109-119
Main Authors: Doi, Hirokazu, Iwasaki, Hiromi, Masubuchi, Yasuhiro, Nishigaki, Ryuichiro, Horie, Toshiharu
Format: Article
Language:English
Subjects:
Animals
Biotransformation
Chemiluminescence
Cimetidine - pharmacology
Cytochrome P-450 Enzyme Inhibitors
Cytochrome P450
Enzyme Inhibitors - pharmacology
Kinetics
Lipid peroxidation
Luminescent Measurements
Male
Microsomes, Liver - drug effects
Microsomes, Liver - metabolism
NADP - metabolism
Oxidation-Reduction
Oxidative stress
Proadifen - pharmacology
Rats
Rats, Wistar
Salicylic acid
Salicylic Acid - pharmacokinetics
TBARS
Thiobarbituric Acid Reactive Substances - metabolism
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Summary:Rat liver microsomal suspension (1 mg protein per ml) was incubated at 37 °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.
ISSN:0009-2797
1872-7786
DOI:10.1016/S0009-2797(02)00004-2