17-ß-estradiol: Antioxidant mechanism on changes induced by neonatal X-radiation.

CACERES, LG; URAN, SL; ZORRILLA ZUBILETE, MA; GUELMAN, LR

Congreso; 41th Annual Meeting of the Society for Neuroscience (SFN); 2011

Ionizing radiation is a physical agent broadly used to kill tumor cells in human cancer therapy. Unfortunately, during the treatment of cerebral tumors, normal brain can undergo undesirable tissue injury. X rays are capable to induce oxidative stress on target tissues, acting mainly through the generation of reactive oxygen species (ROS), common mechanism in animal models of neurodegenerative diseases and neurotoxicity. The elevated vulnerability of the immature brain, together with the limited availability of therapeutic tools to attenuate Central Nervous System (CNS) damage, supports the search and development of new preventive and therapeutic strategies. Interestingly, sex hormones such as estrogens have shown to exert a neuroprotectiverole in models whose pathophysiology involves the generation of oxidative stress.The aim of the present work was to investigate if 17-ß-estradiol (ßE) was able to prevent hippocampal-related behavioral and biochemical changes induced by neonatal ionizing radiation exposure and to elucidate a possible neuroprotective mechanism. Male Wistar rats were irradiated with 5 Gy of X rays between 24 and 48 hours after birth. A subset of rats was subcutaneously administered with successive injections of ßE or 17-α-estradiol (αE), prior and after irradiation. Rats were subjected to different behavioral tasks to evaluate associative memory and anxiety levels. Hippocampal ROS levels and protein kinase C (PKC) activity were also assessed. Results show that hippocampal ROS levels in ßE-treated irradiated rats approached control values as well as the increase in anxiety levels. The changes observed in associative memory of irradiated ratscould not be reversed with the ßE treatment. Moreover, this result is related with the inefficacy of ße administration to prevent radiation-induced hippocampal PKC activity changes. However, the amount of PKC β1, anisozyme regulated by ROS, was restored to control values in the irradiated group. Finally, Eα (an inactive isomer on ßE receptor) administered to irradiated animals was effective in preventing radiation-induced alterations, although with less statistical significance than ßE. In conclusion, results show that ßE was able to counteract most behavioral and biochemical changes induced by X radiation, probably acting through an antioxidant mechanism, as demonstrated in Eαtreated irradiated animals.Since estrogens are widely used therapeutic compounds with a thoroughly evaluated safety profile and in view of the excellent safety history of estrogen therapy, there is sufficient evidence to support the chronic use of estrogen as preventive tools after different CNS insults