The Role of Nitric Oxide in Radiation Damage

Abstract

Free radicals, such as hydrogen and hydroxyl radicals, are produced in aqueous solution after X-irradiation. 1) They react with body tissues and generate lipid peroxidation, DNA lesions and enzyme inactivation, all of which are mediators of radiation damage. [2][3][4][5] Nitric oxide is another free radical induced by irradiation.6,7) Nitric oxide induces vasorelaxation and inhibition of platelet aggregation and thus, can improve hypertension or prevent thrombosis. In contrast, nitric oxide can also have cytotoxic effects. Administration of Nomeganitroarginine methyl ester (L-NAME), which is the nitric oxide synthase (NOS) inhibitor, can prevent enteritis after irradiation. 8) This suggests that nitric oxide may be related to irradiation-induced injury. However, early endothelial injury following radiation exposure causes kidney damage with hypertension, capillary thrombosis and death from renal failure. Hypertension and thrombosis could be caused by a deficit of NOS and indeed, the administration of a nitric oxide emission reagent increases survival time after irradiation. 9) Therefore, it is unclear whether nitric oxide affects protection or injury after irradiation, and its relationship to radiation damage has not been examined.Our continuing research of the radioprotective action of sulfur compounds has been reported over a number of years. [10][11][12][13][14][15] Of the sulfur compounds we have studied, S-2-aminoethylisothiourea 2HBr (AET) 12) is a representative drug in the research of experimental radiation damage protectors. Although AET has an effect on the NOS inhibitor, [16][17][18][19] the relationship between radiation damage protection and inhibition of NOS has not been clarified. This study investigated the role of nitric acid in relation to radiation damage, by examining changes in mouse serum nitrate concentrations after irradiation. The mechanisms of radiation damage protection mediated by AET were also clarified. MATERIALS AND METHODS Laboratory AnimalsFive-week-old male ICR strain mice (Charles River Japan, Inc., Yokohama, Japan) were given nutritional chow (MF; Oriental Yeast Co., Ltd., Tokyo, Japan) and water ad libitum. Mice weighing 32Ϯ3 g (about six-week-old) were used throughout the studies.Irradiation Method Irradiation experiments were carried out by a soft X-ray irradiator (Softex M-100WE; Softex Co., Ltd., Tokyo, Japan). Mice were placed in a circular polystyrene cage (diameter: 150 mm, depth: 23 mm) and covered with a net (mesh: 10 mm), then put on a revolving stage at a distance 400 mm below the source. The animals were wholebody irradiated from the dorsum, using various doses (19.6-31.5 Gy) at 70 kVp, 10 mA, a 10 mm acrylic filter and 0.8 Gy/min. Dose rate of the experiments was determined by a Victoreen model 500 dosimeter, using a model 500-6 A type probe.The irradiation groups were irradiated at doses described in the Results. The non-irradiation group served as a control.Methods for Coordination and Injection of the Drug Lipopolysaccharide E. coli (LPS; Difco Laboratories, D...

Effect of Gamma Ray on Reactive Oxygen Species at Experimental Animals

“…The increase of NO production in irradiated macrophages contributed to tumoricidal activity, with the activation mechanisms differing between high-dose and low-dose irradiation. Our results also in agreement with Ohata et al [31] who investigated the role of nitric oxide in relation to radiation damage, by examining changes in mouse serum nitrate concentrations after irradiation. They reported that post-irradiation serum nitrate concentrations increased dose-dependently with radiation dose, and, claim the known physiological functions of nitric oxide imply that it should prevent radiation-induced death.…”

Radiation Metabolomics. 2. Dose- and Time-Dependent Urinary Excretion of Deaminated Purines and Pyrimidines after Sublethal Gamma-Radiation Exposure in Mice

“…Thus an alternative explanation must be sought. It was reported that γ irradiation of mice results in a statistically significant two- to threefold increase in serum nitrate concentration 2.5–3.0 h postirradiation that returns to baseline after 12 h (32). This nitrate increase is consistent with the effect in mice of sublethal γ -radiation exposure on nitric oxide (NO) synthesis in the liver, intestine, lung, kidney, brain, spleen and heart (33), on increased hepatic nitrite concentration and peroxidative damage (34), and on attenuated hepatic glutathione concentration (34, 35).…”

Thrombospondin-1 and CD47 Limit Cell and Tissue Survival of Radiation Injury

“…11 However, studies using iNOS inducers and NOS inhibitors indicate that elevated NO production can also contribute to radiation injury. 12 Furthermore, NOS2 gene transfer into tumors increased their radiosensitivity, 13 and NOS1-null mice show increased radioresistance in bone marrow.…”