Protective effects of 5,6,7,8-tetrahydroneopterin against X-ray radiation injury in mice

The protective effects of 5,6,7,8-tetrahydroneopterin (NH4) against radiati on injury in mice were studied. (C57BL/6XA/ J)F1 (B6A) mice received a sing le whole-body irradiation dose of 200, 400, 700 or 800 cGy of X-rays. NH4 ( 30 mg/kg body weight) or phosphate-buffered saline (PBS was injected intrap eritoneally into irradiated mice 10 min before and after the irradiation an d again after 6 h. All mice which received the 800 cGy radiation+PBS died b etween 8 and 11 days after the treatment. In contrast, those which also rec eived NH4 demonstrated a significantly prolonged survival time and 40% live d more than 5 months. Total numbers of thymocytes and spleen cells on day 5 post-irradiation were dramatically reduced in line with the radiation dose . The survival was significantly enhanced by NH4 in treated mice. The proli feration of spleen cells in mice stimulated by concanavalin A (Con A) or li popolysaccharide (LPS) was also greater in NH4 treated mice. The immune res ponse of survivors 5 months after 800 cGy+NH4 treatments, against Con A, LP S, allogenic mouse, and sheep red blood cells had essentially recovered to the levels of normal mice. These results indicate that NH4 had an important role in modifying radiation injury. (C) 1999 Elsevier Science B.V. All rig hts reserved.