[Effect of azole derivatives on lucigenin-dependent microsome chemiluminescence].
Both metronidazole and aminotriazole increased while sanazole (drug AK-2123) decreased the NADPH/lucigenin-dependent chemiluminescence of liver microsomes of phenobarbital-treated rats. Sanazole strongly inhibited the lucigenin-dependent chemiluminescence in the enzyme system of xanthine-xanthine oxidase. Aminotriazole and metronidazole were less potent inhibitors of chemiluminescence less than sanazole. All these azole derivatives did not absorb light in the region of light emission of lucigenin. Both lucigenin and sanazole increased the rate of cytochrome c reduction by microsomes in case of using NADPH as a donor of electrons, whereas no effect of metronidazole and aminotriazole on this rate was found. The sanazole inhibition of lucigenin-dependent chemiluminescence could reflect competition between sanazole and lucigenin for electrons in the active centre of flavin reductases. Thus, microsomal NAD(P)H-reductases can be potentially involved in a bioactivation of sanazole. Lucigenin-dependent chemiluminescence cannot be used for measuring the modulating action of agents on reactive oxygen species production in the microsomes, but it may be used for luminometrical studies of enzyme complex NAD(P)H-reductases/cytochrome P450 in model systems.
Shchepetkin
I A
IA
Institute of Oncology, Siberian Branch of the Russian Academy of Medical Sciences, Tomsk, 634001 Russia. oncology@info.tsu.ru
Akhmedzhanov
R R
RR
Kagiia
V T
VT
D000166:Acridines; D000640:Amitrole / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001393:Azoles / Q000378:metabolism / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D008163:Luminescent Measurements; D008297:Male; D008795:Metronidazole / Q000378:metabolism / Q000494:pharmacology; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D009565:Nitrate Reductases / Q000378:metabolism; D051381:Rats; D014230:Triazoles / Q000378:metabolism / Q000494:pharmacology
D000166:Acridines; D001393:Azoles; D007202:Indicators and Reagents; D014230:Triazoles; C072690:AK 2123; D008795:Metronidazole; C033472:10,10'-dimethyl-9,9'-biacridinium; D003577:Cytochrome P-450 Enzyme System; D009565:Nitrate Reductases; D000640:Amitrole