UNIDEF   23986
UNIDAD DE INVESTIGACION Y DESARROLLO ESTRATEGICO PARA LA DEFENSA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
RADIOPROTECTION STUDIES WITH ETHYL PYRUVATE AND ALPHA PHENYL-N-TERT-BUTYLNITRONE (PBN)
Autor/es:
M.E. MACIEL; L.N. QUINTANS; M.H. COSTANTINI; F. FORMOSA LEMOINE; G.D. LÓPEZ; M. MONTALTO DE MECCA; M.I. DÍAZ GÓMEZ; J.A. CASTRO; G.D. CASTRO
Lugar:
Natal
Reunión:
Congreso; 9th Congress of Toxicology in Developing Countries - XIX Congreso Brasileiro de Toxicologia; 2015
Institución organizadora:
IUTOX - Sociedade Brasileira de Toxicologia
Resumen:
The toxic action of ionizing radiation originates in an activation of cell water molecules leading to the production of free radicals and other reactive species. These species react with cellular molecules (DNA, proteins, lipids, etc.), initiating the processes leading to damage. There are compounds with known radioprotective action but showing significant toxic effects (eg. WR-2721). There is an interest in the development of substances or mixtures of substances that may protect against ionizing radiation acute effects with lower toxicity.In this work, we developed an experimental model using Sprague-Dawley rats (both sexes, eight animals per group) exposed to X-radiation at a dose of 2 Gy (whole body). After 48 hours, animals were sacrificed and histology of six locations of the gastrointestinal tract (duodenum, jejunum, ileum, colon, salivary glands) and testis were performed. In addition, leukocyte and erythrocyte count and leukocyte formula were performed. Genetic damage was evaluated by the Comet assay in blood. Survival curves up to 60 days post-irradiation were also performed. The radioprotective effect of alpha phenyl-n-tert-butylnitrone (PBN) at doses of 20 and 40 mg/kg (i.p. in saline, one hour before irradiation) was tested. Separately, ethyl pyruvate was administered as a single dose of 50 mg/kg (i.p. in saline, one hour before irradiation) followed by repeated administration for one month in the drinking water (0.3% v/v). Control groups with the compound under test were run simultaneously.Histology of irradiated animals showed inflammatory processes in the epithelia of the digestive tract and in the testis, with no changes detected in salivary glands. Leukocyte count was drastically reduced compared to the control values, presenting also an altered formula. The effect of PBN on the tested parameters was moderately protective when it was administered at the highest dose, highlighting the recovery of erythrocytes in males and the protection of the epithelium in the small intestine (both sexes) and in the testis. No statistically significant protection in the recovery of the level of leukocytes or leukocyte count were observed (both sexes). The genetic damage revealed in the irradiated animals was not reversed by the treatment with PBN, neither a protective effect for survival was observed at any dose tested. The effect of ethyl pyruvate administration resulted in a protection of the epithelium in the duodenum (both sexes), a statistically significant increase on the survival of females but no protective effect on blood parameters (48 hours).In conclusion, both compounds showed a moderate radioprotective action, that is suitable to be improved by increasing doses or treatment times, due both are substances with low toxicity by themselves.Acknowledgements: Financial support from CITEDEF, grant PIDDEF 11/12 (MINDEF).