STUDY OF PROTECTIVE EFFECTS OF 5,6,7,8-TETRA-HYDRONEOPTERIN AGAINST X-RAY RADIATION INJURY

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The protective effects of 5,6,7,8-tetrahydroneopterin (NPH-4) against radiation injury in mice was studied. (C57BL/6 x A/J) F1 (B6A) mice of received a single whole-body irradiation dose of 200,400,700 or 800 cGy X-rays. NPH-4 (30mg/kg body weight) or BPS were injected intraperitoneally into irradiated mice 10 minutes before and after the irradiation and again after 6 hours. All mice which received the 800 cGy radiation + PBS died between 8 to 11 days after the treatment. In contrast, those that also received NPH-4 demonstrated a significantly prolonged survival time and 40% lived 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 in NPH-4 treated. Proliferation of spleen cells in mice stimulated by concanavilin A (Con A) or lipopolysaccharide (LPS) was also greater in NPH-4 treated mice. The immune response of survivors, 5 months after 800 cGy + NPH-4 treatments, against Con A,LPS,allogeneic mouse, and seep red blood cells (SRBC) had essentially ecovered to the levels of normal mice. These results indicate that NPH-4 had an important role in preventing radiation injury.In conclusion, NPH-4 may be useful as a therapeutic agent against diseases in which active oxygen species act as potent pathogenic factors, such as with post-radiation injury. In particular, NPH-4 might findapplication in combination with radiation therapy for human cancers with poor blood vessel formation such as some pancreatic carcinomas.