Modulatory effect of tempol on toxicity and antitumor activity of 6-mercaptopurine and on P450 cytochrome level

Low sensitivity of contemporary antitumor drugs requires a search for its improvement. In this context, nitroxyl radical 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 (4-oxy--2,2,4,4-tetramethylpiperidine-N-oxyl (tempol) upon its combination 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-mercaptopurine (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. The number of survivors after irradiation at a dose 8.5 Gy and upon addition of tempol is compared. (author)