title: Paraquat- and diquat-induced oxygen radical generation and lipid peroxidation in rat brain microsomes.
abstract: NADPH-menadione reductase activity by rat brain microsomes (Ms) was decreased 40-50% by 10 microM dicumarol, a potent inhibitor of DT-diaphorase, whereas no change in NADPH-paraquat (PQ) and -diquat (DQ) reductase activity was observed. NADPH-DQ reductase activity in brain Ms was 2.5-fold higher than NADPH-PQ reductase activity. The formation of PQ and DQ radicals was verified optically and observed directly by ESR spectroscopy in the NADPH-PQ and -DQ reductase reactions by brain Ms under anaerobic conditions. PQ- and DQ-induced superoxide formation was confirmed by the detection of DMPO-OOH ESR signals and followed by chemiluminescence (CL) of a Cypridina luciferin analogue (CLA). The kinetics and intensity of the CL were consistent with the observations that the reduction in DQ is faster than that in PQ. Thiobarbituric acid reactive substances (TBARS) and phospholipid hydroperoxides in brain Ms increased in the presence of NADPH and Fe3+. The generation of both lipid peroxidation products derived from brain Ms decreased with increasing concentrations of PQ and DQ. The inhibitory effect of DQ is more pronounced than that of PQ. The formation of PQ- and DQ-induced reactive oxygen species was not associated with lipid peroxidation in rat brain Ms.
authors.affiliation: Division of Biophysics, Institute for Electronic Science, Hokkaido University, Sapporo 060-8638, Japan.
authors.forename: Kunio
authors.initials: K
authors.lastname: Yumino
authors.forename: Ikuo
authors.initials: I
authors.lastname: Kawakami
authors.forename: Mamoru
authors.initials: M
authors.lastname: Tamura
authors.forename: Takaaki
authors.initials: T
authors.lastname: Hayashi
authors.forename: Masao
authors.initials: M
authors.lastname: Nakamura
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002384:Catalysis; D004178:Diquat / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005609:Free Radicals; D006540:Herbicides / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000378:metabolism; D015227:Lipid Peroxidation; D008861:Microsomes / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D010269:Paraquat / Q000494:pharmacology*; D010300:Parkinson Disease / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D017392:Thiobarbituric Acid Reactive Substances; D013997:Time Factors
chemical_list: D005609:Free Radicals; D006540:Herbicides; D010743:Phospholipids; D017392:Thiobarbituric Acid Reactive Substances; D004178:Diquat; D006861:Hydrogen Peroxide; D010269:Paraquat; D010100:Oxygen