The role of nitric oxide in radiation damage.
This study investigated the role of nitric oxide in radiation-induced damage by examining changes in mouse serum nitrate concentrations after irradiation. In addition, the contribution of S-2-aminoethylisothiourea 2HBr (AET) to the mechanisms of radiation damage protection was also clarified. The serum nitrate concentration increased as soon as 1.5 h after irradiation, and after 2.5 to 3.0 h the concentrations were significantly higher compared with normal levels. Normal levels were re-established after 12 h. Post-irradiation serum nitrate concentrations increased dose-dependently with irradiation dose (19.6-31.5 Gy). AET suppressed increases in the serum nitrate concentration following irradiation while 2-mercaptoethylamine HCl (MEA) did not. AET has an inhibitory effect on inducible nitric oxide synthase (iNOS); therefore, the increase in nitric oxide after irradiation may be produced by iNOS. Combined administration of irradiation and lipopolysaccharide (LPS) induced a significant increase in serum nitrate concentration, and a significant decrease in survival rate, compared with irradiation alone. The administration of AET or aminoguanidine increased survival rate following irradiation. In contrast to findings after LPS administration, IL-1beta and IFN-gamma were not determined in serum following irradiation. Existing iNOS is activated by irradiation, and nitric oxide production appears to increase without iNOS induction. Thus, the irradiation-induced increase in nitric oxide may be related to lethal injury.
Ohta
Setsuko
S
Department of Biology, Faculty of Pharmaceutical Sciences, Hoshi University, Tokyo, Japan. ohta@hoshi.ac.jp
Matsuda
Shinji
S
Gunji
Mihoko
M
Kamogawa
Asahi
A
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004307:Dose-Response Relationship, Radiation; D006146:Guanidines / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009566:Nitrates / Q000097:blood / Q000528:radiation effects*; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000235:genetics / Q000528:radiation effects; D011829:Radiation Dosage; D011837:Radiation-Protective Agents / Q000494:pharmacology; D013997:Time Factors; D014916:Whole-Body Irradiation; D000338:beta-Aminoethyl Isothiourea / Q000494:pharmacology
D006146:Guanidines; D008070:Lipopolysaccharides; D009566:Nitrates; D011837:Radiation-Protective Agents; D000338:beta-Aminoethyl Isothiourea; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C004479:pimagedine