DEFEROXAMINE ANTIOXIDANT ACTIVITY ON CEREBELLAR GRANULE CELLS GAMMA-IRRADIATED IN VITRO

GUELMAN, LAURA RUTH; PAGOTTO, ROMINA MARÍA DEL LUJÁN; DI TORO, CECILIA GABRIELA; ZIEHER, LUIS MARÍA

NEUROTOXICOLOGY AND TERATOLOGY.

Elsevier

Año: 2004 vol. 26 p. 477 - 483

0892-0362

Oxidative stress has been implicated in the pathogenesis of many neurodegenerative and neurological disorders, with reactive oxygenspecies (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-inducedoxidative 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 g radiation, and 30 ? 60 min before irradiation, deferoxamine (Dfx), aniron 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 ROSincrease 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 incultures of cerebellar granule cells, being ROS-induced oxidative damage one of the mechanisms through which radiation might induce celldeath. Therefore, blocking ROS production through the use of a chelating agent, such as Dfx, would be a useful therapeutic tool in differentexperimental models.