Estradiol valerate and tibolone: effects upon brain oxidative stress and blood biochemistry during aging in female rats

Estrogen compounds have been described as important brain protectors. This study investigated the effects of estradiol valerate (EV-0.3 mg/kg) and two concentrations of tibolone (TB1 = 0.5 mg/kg and TB2 = 1 mg/kg) on brain oxidative stress parameters and blood biochemistry in ovariectomized female rats, of three different age groups (young-2 months, adult-8 months, and old-20 months). In the brain cortex, young and old TB2-treated and old no-hormone-replacement (NR) females showed lower lipid hydroperoxide (LPO) levels compared to young Sham and adult TB1 animals (P < 0.05). Also in the cortex, both tibolone doses produced higher (P < 0.05) total antioxidant capacity (TOSC) levels compared to EV-treated adult females. Ovariectomized adult females (NR, EV, TB1 and TB2) showed lower (P < 0.05) TOSC levels in the hippocampus compared to the Sham control. Reactive oxygen species (ROS) were higher (P < 0.05) in old females compared to all younger ones. TB2-treated adults showed higher plasma glucose (P < 0.05) levels compared to old animals. Regardless of age, TB2 treatment increased female (P < 0.05) LDL levels compared to Sham and EV-treated animals. In old females, TB2 significantly increased HDL levels compared to Sham controls, and decreased triglyceride levels were shown in EV, TB1 and TB2 compared to Sham old females. The Atherogenic Index of Plasma was higher (P < 0.05) in adult tibolone-treated females compared to both young and old TB2-treated females. These results suggest that the effects of gonad steroid on brain and blood physiology change significantly with aging, and that evaluating hormonal treatment types and doses could be the key factor in the potential use of a specific hormone therapy.