title: Early changes in L-arginine-nitric oxide metabolic pathways in response to the whole-body gamma irradiation of rats.
abstract: OBJECTIVE
  Nitric oxide (NO), a reactive radical, is formed in higher amounts from L-arginine by inducible NO synthase (iNOS) during early response to ionizing radiation presumably as a part of signal transduction pathways. This study investigated the changes in L-arginine-NO metabolic pathways within a 24-hour period after whole-body gamma irradiation of rats with the range of low to supra-lethal doses.
  
  
  METHODS
  Young adult female Wistar rats received either 0-50 Gy whole-body irradiation or an intraperitoneal injection of bacterial lipopolysaccharide (LPS, 10 mg/kg). Exhaled NO was monitored using chemiluminiscence, nitrite + nitrate (NO(x)) and L-arginine were assayed by high-performance liquid chromatography, and expression of iNOS was determined using Western blot.
  
  
  RESULTS
  Irradiation resulted in a dose-dependent increase of plasma NO(x) to maximum levels which were 4-fold higher compared to controls (p < 0.001). The NO(x) levels increased less in the bronchoalveolar lavage fluid (BAL) (1.7-fold, p < 0.001) and liver homogenate (2.5-fold, p < 0.05), respectively, and were dose-independent. Exhaled NO, lung NO(x), plasma and BAL L-arginine, and the expression of iNOS in lung and liver tissues of irradiated rats and controls were similar. LPS caused a considerable increase (p < 0.001) in exhaled NO (61-fold), NO(x) levels (plasma 34-fold, BAL 6-fold, lung 5-fold, liver 4-fold), and in iNOS expression, respectively.
  
  
  CONCLUSIONS
  In contrast to the LPS treatment of rats, the radiation-induced changes in L-arginine-NO metabolic pathways are modest, particularly in the airways and lungs. Noninvasive measurement of exhaled NO within a 24-h period following the exposure of rats to ionizing radiation has no value for biodosimetry.
authors.affiliation: Department of Medical Biochemistry, Faculty of Medicine in Hradec Králové, Charles University in Prague, Faculty of Medicine in Hradec Králové, Hradec Králové, Czech Republic.
authors.forename: Andrea
authors.initials: A
authors.lastname: Babicova
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Havlinova
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Pejchal
authors.forename: Ales
authors.initials: A
authors.lastname: Tichy
authors.forename: Martina
authors.initials: M
authors.lastname: Rezacova
authors.forename: Jirina
authors.initials: J
authors.lastname: Vavrova
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Chladek
mesh_terms: D000818:Animals; D001120:Arginine / Q000378:metabolism / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D004790:Enzyme Induction / Q000528:radiation effects; D005260:Female; D005720:Gamma Rays; D053858:Metabolic Networks and Pathways; D009569:Nitric Oxide / Q000378:metabolism / Q000528:radiation effects*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism / Q000528:radiation effects; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014916:Whole-Body Irradiation
chemical_list: D009569:Nitric Oxide; D001120:Arginine; D052247:Nitric Oxide Synthase Type II