TIME COURSE OF GSH REDUCTASE ACTIVITY IN NEONATAL RAT CEREBELLUM IRRADIATED AT BIRTH

DI TORO, PATRICIA A; ZIEHER, LUIS M; DI TORO, CECILIA G.; GUELMAN, LAURA R

Washington DC, USA

Congreso; 35th Annual Meeting of the Society for Neuroscience (SFN); 2005

Society for Neuroscience

Exposure of neonatal rats to ionizing radiation induces cellular damage, mainly through generation of reactive oxygen species (ROS). Developing tissues, such as CNS, are more vulnerable to ROS-induced damage. In particular, developing cerebellum has been reported to be sensitive to ROS-induced, radiation-mediated injury. Since glutathione (GSH), an endogenous antioxidant, is able to neutralize these toxic compounds through a process of autooxidation to oxydized glutathione (GSSG), the aim of the present work was to investigate if glutathione reductase (GSHr), the enzyme responsible for reducing GSSG to GSH, is involved in the generation of the previously described radiation-induced changes in cerebellar GSH levels. Neonatal Wistar rats were irradiated in their cephalic ends with 5 Gy of gamma radiation within 48 hs from birth. Cerebellar GSH levels and cerebellar GSHr activity were determined at 1h and 1, 20, 30, 90 and 180 days post-irradiation (PI). Results show that ionizing radiation induced a decrease in cerebellar GSH levels at 1 day PI, increasing through time over controls values. This time course was not accompanied by parallel changes in cerebellar GSHr activity; on the contrary, its activity remains at 80% of control values over all ages tested. These results suggest that GSHr would not be involved in radiation-induced cerebellar GSH changes. This suggestion is supported by the high correlation between total cerebellar GSHr levels and cerebellar weight (r2= 0,9), demonstrating that the observed changes in cerebellar GSHr activity might be mainly related to cerebellar atrophy.