Enhanced oxidative stress in female rat brain after gonadectomy

Oxidative stress, assessed by tissue ascorbate loss following ischemia, is greater in male than female rat brain. The factors mediating this gender difference are unclear. The goal of the present studies was to determine the influence of gonadal sex hormones on this difference. Three weeks prior to experiment, adult Long-Evans male and female rats were gonadectomized for comparison with controls. Ascorbate and glutathione levels were determined in brain and plasma under basal conditions and in brain after one-hour decapitation ischemia, using liquid chromatography with electrochemical detection. Basal ascorbate levels in brain were 6-9% higher in males than in females, whereas plasma levels were 100% higher in males. After gonadectomy, the gender difference in plasma ascorbate levels was lost, while the effect on basal brain levels depended upon region. Ischemia-induced losses in brain ascorbate were three-fold greater in control males compared to control females. Significant losses occurred in frontal cortex, hippocampus, and cerebellum in males during ischemia, whereas loss in females was significant in cerebellum only. After gonadectomy, increased ascorbate loss was seen in all female brain regions, indicating enhanced oxidative stress. This increase eliminated the gender difference in loss; male ascorbate loss was comparatively unaffected by gonadectomy. Glutathione levels and loss were unaffected by either gender or gonadectomy, indicating differences in regulation from that of ascorbate. These findings provide evidence for the hypothesis that protection against oxidative stress is afforded by ovarian sex hormones, thus decreasing the potential for oxidative cell damage in females compared to males.