Study of the ability of a new nitric oxide synthase inhibitor INOS1 to selectively protect the normal tissue in the Ehrlich carcinoma radiotherapy model

The article presents the ability of the new NOS inhibitor named INOS1, N,S-substituted isothiourea derivative, to selectively protect the normal tissues on the model of Ehrlich solid carcinoma radiotherapy in mice. A single injection of INOS1 (75 mg/kg, ¼ LD16) 30 min before local single-dose (30 Gy) or hypofractionated (20+20 Gy) radiation exposure significantly reduced the radiation alteration of normal tissues and the clinical and morphological severity of acute radiation reactions. The substance did not modify the effects of gamma-radiation on the tumor, grafted on mouse limb, and did not reduce therapeutic effect. Transient suppression of endogenous NO synthesis led to protection of normal tissues exposed to radiation, however, it did not change the radiosensitivity of solid tumor tissues. The results allow authors to consider NOS inhibitors, in particular INOS1, as the promising basis for development of pharmaceuticals for prevention of radiotherapy-induced complications.