Modulatory effect of tempol on toxicity and antitumor activity of 6-mercaptopurine and on P450 cytochrome level.
Low selectivity of contemporary antitumor drugs requires a search for its improvement. In this context, nitroxyl radicals are of interest as promising pharmacological agents. The introduction of nitroxyl radical into the structure of antitumor cytostatics was found to reduce considerably their general and specific toxicity. In this work, we demonstrate a detoxifying effect of tempol upon its combined injection with cytostatics at their absolute lethal dose in the intact mice as well as an improvement of sensitivity of tumor-bearing animals to 6-MP. Tempol is shown to normalize the level of oxidized form of P450 cytochrome in a liver, reduced as a result of the injection of 6-MP.
Konovalova
N P
NP
Institute of Chemical Physics, Russian Academy of Sciences, Chernogolovka, Moscow Region, Russia.
Diatchkovskaya
R F
RF
Volkova
L M
LM
Varfolomeev
V N
VN
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects* / Q000378:metabolism; D004357:Drug Synergism; D005260:Female; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000201:enzymology*; D015122:Mercaptopurine / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013113:Spin Labels
D000964:Antimetabolites, Antineoplastic; D003497:Cyclic N-Oxides; D013113:Spin Labels; D003577:Cytochrome P-450 Enzyme System; D015122:Mercaptopurine; C001803:tempol