IONIZING RADIATION-INDUCED DAMAGE ON DEVELOPING CEREBELLAR GRANULE CELLS CULTURES CAN BE PREVENTED BY AN EARLY AMIFOSTINE POST-TREATMENT

GUELMAN, L. R; CABANA, J.I.; PAGOTTO, R. M. L; ZIEHER, L. M.

INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE

Elsevier

Año: 2005 vol. 23 p. 1 - 7

0736-5748

Developing central nervous system (CNS) is highly sensitive to ionizing radiation due, in part, to reactive oxygen species (ROS) damage.A variety of compounds able to protect brain cells essentially by decreasing ROS production have been widely used to confirm ROSparticipation in different mechanisms of brain injury, as well as to evaluate them as therapeutic tools.To test if ionizing radiation-induced damage on immature cerebellar granule cells is mainly mediated by ROS accumulation, a free radicalscavenger ?amifostine (amf) ? was used in an in vitro model. Moreover, the amf therapeutic effect was investigated.Results show that only an early (20?30 min) post-treatment with amf, acting through an antioxidant mechanism, has been effective inpreventing cerebellar granule cell loss observed after ionizing radiation exposure in vitro.These data suggest that immature cerebellar granule cells grown in vitro are highly vulnerable to ROS damage and that a therapeuticintervention could be effective in a narrow temporal window. Moreover, radiation-induced cell death can be partially prevented by a completelimitation of ROS generation, suggesting that other mechanisms besides oxidative stress would also be responsible for the cellular damagefound in this model.