title: Ionizing radiation-induced damage on developing cerebellar granule cells cultures can be prevented by an early amifostine post-treatment.
abstract: 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 ROS participation 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 radical scavenger--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 in preventing 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 therapeutic intervention could be effective in a narrow temporal window. Moreover, radiation-induced cell death can be partially prevented by a complete limitation of ROS generation, suggesting that other mechanisms besides oxidative stress would also be responsible for the cellular damage found in this model.
authors.affiliation: 1 Cátedra de Farmacología, Facultad de Medicina, UBA, Paraguay 2155, piso 15, 1121 Buenos Aires, Argentina. lguelman@fmed.uba.ar
authors.forename: Laura Ruth
authors.initials: LR
authors.lastname: Guelman
authors.forename: Javier Ignacio
authors.initials: JI
authors.lastname: Cabana
authors.forename: Romina María
authors.initials: RM
authors.lastname: del Luján Pagotto
authors.forename: Luis María
authors.initials: LM
authors.lastname: Zieher
mesh_terms: D004999:Amifostine / Q000008:administration & dosage*; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D002452:Cell Count / Q000379:methods; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000254:growth & development; D009474:Neurons / Q000187:drug effects* / Q000528:radiation effects*; D011832:Radiation Injuries / Q000517:prevention & control*; D011839:Radiation, Ionizing; D011837:Radiation-Protective Agents / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors
chemical_list: D011837:Radiation-Protective Agents; D017382:Reactive Oxygen Species; D004999:Amifostine