Radiation biology. Radioecology
ISSN: 0869-8031

Archives → 2018 → Vol. 58, No. 6 → pp. 597-607

Article

Radioprotective Effects in Combined Use of NO-SynthaseInhibitor T1023 and Mexamine

Filimonova M.V., Makarchuk V.M., Filimonov A.S., Chesnakova E.A., Shevchenko L.I., Shevchuk A.S., Surinova V.I.

A. Tsyb Medical Radiological Research Center – branch of National Medical Research Center of Radiology of the Ministry of Health of Russia, Obninsk, Russia

Abstract

The studies aimed at testing spleen endo- and exocolonies have shown that the combined use of compound T1023 at doses of 25–75 mg/kg and mexamine at doses of 5–20 mg/kg causes an equally effective radioprotective effect close to the maximum possible (DRF 2.9–3.1 and 3.0). Such use of T1023 and mexamine at optimal radioprotective doses (75 and 20 mg/kg) leads to the realization of an anti-radiation effect with limited, additive interaction of radioprotectors. However, in the case of using T1023 and mexamine at low doses (25 and 5 mg/kg), a significant 2-fold enhanced radioprotective effect was achieved after a pronounced syner-gistic interaction of these radioprotectors. It was found that a combined use of T1023 (25 mg/kg) and me-xamine (5 mg/kg) provides a 100% 30-day survival of irradiated mice exposed to doses up to 10 Gy and a 30–40% survival rate at doses of 11–13 Gy. The DRF index is 1.73, which is 20–30% higher than for the optimal radioprotective doses of T1023 and mexamine administered separately. It was found that there was no increase in the «acute» toxicity of T1023 and mexamine after their combined administration. These data allows us to consider the combined use of NOS inhibitor T1023 and mexamine as a promising basis for the development of more effective and safe emergency radioprotectors.

Keywords

isothiourea derivatives, nos inhibitors, indolylalkylamine derivatives, radio-protective action, pharmacodynamics interaction