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Biol Pharm Bull ; 30(6): 1102-7, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17541161

ABSTRACT

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.


Subject(s)
Nitrates/radiation effects , Nitric Oxide/metabolism , Whole-Body Irradiation , Animals , Cell Survival/drug effects , Dose-Response Relationship, Radiation , Guanidines/pharmacology , Lipopolysaccharides/toxicity , Male , Mice , Mice, Inbred ICR , Nitrates/blood , Nitric Oxide Synthase Type II/antagonists & inhibitors , Nitric Oxide Synthase Type II/genetics , Nitric Oxide Synthase Type II/radiation effects , Radiation Dosage , Radiation-Protective Agents/pharmacology , Time Factors , beta-Aminoethyl Isothiourea/pharmacology
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