RADIOPROTECTIVE EFFECT OF ETHYL PYRUVATE ALONE OR AS A COADYUVANT OF AMIFOSTINE

G.D. CASTRO; M.I. DÍAZ GÓMEZ; M. MONTALTO DE MECCA; M.E. MACIEL; M.H. COSTANTINI; G.D. LÓPEZ; L.N. QUINTANS; F. FORMOSA LEMOINE; J.A. CASTRO

Merida

Congreso; XIV International Congress of Toxicology - X Mexican Congress of Toxicology; 2016

IUTOX - SOMTOX

Radiation-induced cellular damage is attributed primairly to the harmful effects of free radicals. Molecules having free radical-scavenging properties are particularly promising as radioprotectors. Among the currently available radioprotectors, only amifostine has been shown in clinical trials to reduce radiation-induced toxicity. This compound is an efficient radioprotector but exhibit some undesirable side effects which prevent its repetitive use. Our efforts are directed to develop radioprotective agents having lower toxicity, own protective potential or suitable as coadyuvant of amifostine. In the present studies we describe results obtained by repetitive oral administration of ethyl pyruvate (EP).Eight male or female groups of Sprague-Dawley rats were exposed (whole body) to a X ray dose of 2 Gy. After that, short term or long term experiments were performed. Control groups were run simultaneously. Short term: 48 hours after radiation exposure samples were obtained for histology (duodenum, jejunum, ileum, colon, salivary glands and testes). In addition, erythrocyte and leukocyte count and formula were measured. Occurrence of genotoxic effects in blood leukocytes was evaluated by the Comet assay. Preventive effects of EP were tested by administrating it as a single dose of 50 mg/kg i.p. in saline one hour before irradiation. Long term: Survival studies were performed treating animals with amifostine (100 mg/kg, i.p.) half hour before irradiation, or with a single dose of EP (50 mg/kg) one hour before irradiation, followed in both cases by repetitive adminstration of EP as a 0.3% v/v solution in drinking water for one month.Results: Histology of irradiated animals showed inflammatory processes in the epithelia of the digestive tract and in testis, with no changes detected in salivary glands. Leukocyte count was drastically reduced compared to control, presenting also an altered formula. The effect of EP resulted in a protection of the epithelium in the duodenum and a partial protective effect on blood parameters (males). Genetic damage was significantly reversed by treatment with EP or EP plus amifostine (both sexes), and also a protective effect for survival was observed only in females. In conclusion, EP showed a moderate but significant radioprotective action, that could be improved by increasing dose or treatment time, considering EP has a low toxicity by itself.Acknowledgements: Grant PIDDEF 11/12 (MINDEF).