Sensitivity of cerebellar glutathione system to neonatal ionizing radiation exposure.
Reactive oxygen species (ROS) are relevant components of living organisms that, besides their role in the regulation of different important physiological functions, when present in excess are capable to affect cell oxidative status, leading to damage of cellular molecules and disturbance of normal cell function. ROS accumulation has been associated with a variety of conditions such as neurodegenerative diseases and ionizing radiation exposure. Cell ability to counteract ROS overproduction depends on the capacity of the endogenous antioxidant defenses--which includes the glutathione (GSH) system--to cope with. Since developing central nervous system (CNS) is especially sensitive to ROS-induced damage, the aim of the present work was to evaluate ROS, reduced GSH and oxidized glutathione (GSSG) levels in the cerebellum at different developmental ages after irradiation, in order to test if any changes were induced on these key oxidative stress-related cellular markers that might explain the high cerebellar vulnerability to radiation-induced injury. Since intracellular levels of GSH are maintained by glutathione reductase (GSHr), this enzymatic activity was also evaluated. Newborn Wistar rats were irradiated in their cephalic ends and the different parameters were measured, from 1h to 90 days post-irradiation. Results showed that an early transient increase in ROS levels followed by a decrease in cerebellar weight at 3-5 days post-irradiation were induced. An increase in cerebellar GSH levels was induced at 30 days after irradiation, together with a decrease in GSHr activity. These results support the hypothesis that ROS may represent a marker of damage prior to radiation-induced cell death. In contrast, it would be suggested that GSH system might play a role in the compensatory mechanisms triggered to counteract radiation-induced cerebellar damage.
Di Toro
C G
CG
1a Cátedra de Farmacología, Facultad de Medicina, UBA, Buenos Aires, Argentina.
Di Toro
P A
PA
Zieher
L M
LM
Guelman
L R
LR
D000375:Aging / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D002531:Cerebellum / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects*; D005260:Female; D005720:Gamma Rays; D005978:Glutathione / Q000378:metabolism*; D005980:Glutathione Reductase / Q000378:metabolism; D008297:Male; D009929:Organ Size / Q000528:radiation effects; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism
D017382:Reactive Oxygen Species; D005980:Glutathione Reductase; D005978:Glutathione