Deferoxamine antioxidant activity on cerebellar granule cells gamma-irradiated in vitro.
Oxidative stress has been implicated in the pathogenesis of many neurodegenerative and neurological disorders, with reactive oxygen species (ROS) as part of the intracellular effectors of damage formed in the presence of an excess of iron. Ionizing radiation induces tissue damage on developing CNS through different simultaneous mechanisms, including ROS-induced oxidative damage; therefore, exogenously added iron chelators might contribute to protect cells from free-radical injury. Cerebellar granule cells grown in vitro were exposed to 0.3 Gy of gamma radiation, and 30-60 min before irradiation, deferoxamine (Dfx), an iron chelator, was added at different nontoxic concentrations. When cell viability and ROS levels were evaluated in Dfx-treated cultures, a partial prevention of radiation-induced cell death and ROS increase were found, being this prevention concentration independent. These data support the involvement of an iron-driven hydroxyl radical formation pathway in the acute toxic mechanism of radiation in cultures of cerebellar granule cells, being ROS-induced oxidative damage one of the mechanisms through which radiation might induce cell death. Therefore, blocking ROS production through the use of a chelating agent, such as Dfx, would be a useful therapeutic tool in different experimental models.
Guelman
Laura Ruth
LR
1a Cátedra de Farmacología and Instituto de Neurociencias Aplicadas, Facultad de Medicina, UBA, Paraguay 2155, piso 15 (1121) Buenos Aires, Argentina. lguelman@fmed.uba.ar
Pagotto
Romina María del Luján
RM
Di Toro
Cecilia Gabriela
CG
Zieher
Luis María
LM
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000494:pharmacology*; D002452:Cell Count / Q000379:methods; D016923:Cell Death / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology*; D003676:Deferoxamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005720:Gamma Rays / Q000009:adverse effects*; D008297:Male; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000528:radiation effects*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism
D000975:Antioxidants; D017382:Reactive Oxygen Species; D003676:Deferoxamine