Lipid peroxidation and chemiluminescence during naproxen metabolism in rat liver microsomes.
1. Rat liver microsomal suspension containing NADPH and MgCl2 was incubated at 37 degrees C with naproxen, a non-steroidal anti-inflammatory drug. Thiobarbituric acid reactive substances (TBA-RS), high molecular weight protein aggregates and fluorescent substances were formed in the microsomal suspension. 2. Chemiluminescence was produced from the microsomal suspension. This chemiluminescence production was well correlated to the TBA-RS formation, indicating that the chemiluminescence production was closely associated with the lipid peroxidation. 3. The addition of SKF-525A to the microsomal suspension inhibited the production of TBA-RS, chemiluminescence and 6-demethylnaproxen (6-DMN), the oxidative product of naproxen. Further, the antioxidant, alpha-tocopherol and singlet oxygen quenchers like histidine, dimethylfuran and 1,4-diazabicyclo[2,2,2]octane strikingly inhibited the productions of chemiluminescence and TBA-RS. 4. Neither naproxen nor 6-DMN caused lipid peroxidation in the absence of NADPH. Thus, lipid peroxidation and chemiluminescence during the oxidation of naproxen in liver microsomes was suggested to be provoked by reactive oxygen species and an origin of chemiluminescence was shown to be singlet oxygen.
Yokoyama
H
H
Department of Biopharmaceutics, Tokyo College of Pharmacy, Japan.
Horie
T
T
Awazu
S
S
D000818:Animals; D016587:Antimutagenic Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D003035:Cobalt / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D005296:Ferrous Compounds / Q000494:pharmacology; D006639:Histidine / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects*; D008163:Luminescent Measurements; D015636:Magnesium Chloride / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism; D008970:Molecular Weight; D009249:NADP / Q000378:metabolism; D009288:Naproxen / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D010882:Piperonyl Butoxide / Q000494:pharmacology; D011335:Proadifen / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology
D016587:Antimutagenic Agents; D000975:Antioxidants; D005296:Ferrous Compounds; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D015636:Magnesium Chloride; D014810:Vitamin E; C020748:ferrous sulfate; D003035:Cobalt; D006639:Histidine; D009249:NADP; D009288:Naproxen; D011335:Proadifen; C018021:cobaltous chloride; D010882:Piperonyl Butoxide; D001205:Ascorbic Acid; C034451:desmethylnaproxen