title: In vivo study of radioprotective effect of NO-synthase inhibitors and acetyl-L-carnitine.
abstract: This study investigated the protective effect of two nitric oxide synthase inhibitors N(omega)-nitro-L-arginine methyl ester (L-NAME, 100 mg/kg i.p.) and aminoguanidine (AG, 400 mg/kg i.p.), and an antioxidant acetyl-L-carnitine (ALC, 250 mg/kg i.p., once daily for five days) against radiation-induced damage in Wistar rats. Blood samples were collected 6 h after whole-body irradiation with 8 Gy. Plasma concentrations of nitrite+nitrate (NO(x)) and malondialdehyde (MDA) were measured by high-performance liquid chromatography. A single injection of L-NAME one hour before exposure effectively prevented the radiation-induced elevation of plasma NO(x) and it reduced 2.6-fold the risk for death during the subsequent 30-day period. Pretreatment with ALC prevented the radiation-induced increase in plasma MDA and it had similar effect on mortality as L-NAME did. Presumably due to its short half-life, the partially iNOS-selective inhibitor and antioxidant AG given in a single dose before exposure did not attenuate MDA and NO(x) and it failed to significantly improve the 30-day survival. In conclusion, pretreatment with both the nonspecific NOS inhibitor L-NAME and the antioxidant ALC markedly reduce mortality to radiation sickness in rats. The radioprotective effect may be directly related to effective attenuation of the radiation-induced elevation of NO production by L-NAME and of oxidative stress by ALC.
authors.affiliation: Department of Medical Biochemistry, Charles University, Faculty of Medicine, Hradec Kralove, Czech Republic. babicovaa@gmail.com.
authors.forename: A
authors.initials: A
authors.lastname: Babicová
authors.forename: Z
authors.initials: Z
authors.lastname: Havlínová
authors.forename: M
authors.initials: M
authors.lastname: Hroch
authors.forename: M
authors.initials: M
authors.lastname: Rezáčová
authors.forename: J
authors.initials: J
authors.lastname: Pejchal
authors.forename: J
authors.initials: J
authors.lastname: Vávrová
authors.forename: J
authors.initials: J
authors.lastname: Chládek
mesh_terms: D000108:Acetylcarnitine / Q000627:therapeutic use*; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D005260:Female; D006146:Guanidines / Q000627:therapeutic use*; D019331:NG-Nitroarginine Methyl Ester / Q000627:therapeutic use*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D011832:Radiation Injuries / Q000503:physiopathology / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000975:Antioxidants; D006146:Guanidines; D011837:Radiation-Protective Agents; D000108:Acetylcarnitine; D019001:Nitric Oxide Synthase; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester