[Effect of platinum derivatives on microsomal NADPH-oxidoreductase activity].
The influence of platinum derivatives, cisplatin (cis-diamminedichloroplatinum) and imidazolplatin (cis-diimidazoledichloroplatinum) on the activity of rat liver microsomal NADPH-oxidoreductases was investigated in vitro using spectrophotometrical and chemiluminometrical methods. In the range of concentrations from 1 to 12 microM cisplatin inhibited NADPH-cytochrome c-reductase activity and NADPH/lucigenin-dependent chemiluminescence of microsomes. The 3 microM cisplatin decreased the NADPH-dependent reductase activity by 50%. At concentrations less than 2.5 mM sanazole (drug AK-2123) did not prevent the inhibiting influence of cisplatin on microsomal NADPH-dependent reductases. Imidazolplatin insignificantly inhibited NADPH-reductases. It is concluded that negligible inhibiting effect of imidazolplatin on microsomal NADPH-oxidoreductase allows us to consider this platinum derivative as a promising compound for further experimental trials as anticancer drug with low toxic action on the normal tissues of an organism.
Shchepetkin
I A
IA
Institute of Oncology, Tomsk Research Center, Siberian Branch of Russian Academy of Medical Sciences, per. Kooperativnyi 5, Tomsk 634001, Russia.
Plotnikov
V M
VM
Kagiia
V T
VT
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002945:Cisplatin / Q000494:pharmacology*; D003574:Cytochrome c Group / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D008163:Luminescent Measurements; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism*; D009245:NADH Dehydrogenase / Q000378:metabolism*; D017671:Platinum Compounds / Q000494:pharmacology*; D051381:Rats
D000970:Antineoplastic Agents; D003574:Cytochrome c Group; D007093:Imidazoles; D017671:Platinum Compounds; C439848:diimidazoldichloroplatinum; D009245:NADH Dehydrogenase; D002945:Cisplatin