Superoxide anion production during monoelectronic reduction of xenobiotics by preparations of rat brain cortex, microvessels, and choroid plexus.
Brain microsomes may produce reactive metabolites during the reductive metabolism of some xenobiotics including drugs. These reactive species can, in turn, react with molecular oxygen to form superoxide radicals (O2.-). We measured the rates of superoxide production by homogenates obtained from three cerebral structures, cortex plus cerebellum, choroid plexus, and microvessels. The molecules assayed were related to quinone, nitroheterocycle, and iminium chemical families. The results we obtained showed a significant correlation between the rate of superoxide anion production and the apparent kinetic parameters (log Km/Vmax) of NADPH-cytochrome P450 reductase activity for these molecules, suggesting the involvement of this enzyme in xenobiotic-induced superoxide production.
Lagrange
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P
CNRS URA 597, Centre du Médicament, Nancy, France.
Livertoux
M H
MH
Grassiot
M C
MC
Minn
A
A
D000818:Animals; D002531:Cerebellum / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism*; D002560:Cerebrovascular Circulation; D002831:Choroid Plexus / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008833:Microcirculation / Q000378:metabolism; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species; D013329:Structure-Activity Relationship; D013481:Superoxides / Q000378:metabolism*; D015262:Xenobiotics / Q000378:metabolism*
D017382:Reactive Oxygen Species; D015262:Xenobiotics; D013481:Superoxides; D009251:NADPH-Ferrihemoprotein Reductase