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 radiation injury in mice were studied. (C57BL/6xA/J)F1 (B6A) mice received a single 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 intraperitoneally into irradiated mice 10 min before and after the irradiation and again after 6 h. All mice which received the 800 cGy radiation+PBS died between 8 and 11 days after the treatment. In contrast, those which also received NH4 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 NH4 in treated mice. The proliferation of spleen cells in mice stimulated by concanavalin A (Con A) or lipopolysaccharide (LPS) was also greater in NH4 treated mice. The immune response of survivors 5 months after 800 cGy+NH4 treatments, against Con A, LPS, 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.
Yasumura
M
M
Department of Gastroenterological Surgery, Aichi Cancer Center, 1-1 Kanokoden, Chikusa-ku, Nagoya 4648681, Japan.
Morimoto
T
T
Takagi
M
M
Hirose
H
H
Taguchi
O
O
D000818:Animals; D001708:Biopterins / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002452:Cell Count; D002455:Cell Division; D002478:Cells, Cultured; D003208:Concanavalin A; D004307:Dose-Response Relationship, Radiation; D008070:Lipopolysaccharides; D016131:Lymphocyte Subsets; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011833:Radiation Injuries, Experimental / Q000188:drug therapy* / Q000276:immunology; D011837:Radiation-Protective Agents / Q000627:therapeutic use*; D013154:Spleen / Q000276:immunology; D015996:Survival Rate; D013950:Thymus Gland / Q000276:immunology; D014916:Whole-Body Irradiation
D008070:Lipopolysaccharides; D011837:Radiation-Protective Agents; D003208:Concanavalin A; D001708:Biopterins; C023455:tetrahydroneopterin