Vitamin A supplementation at clinical doses induces a dysfunction in the redox and bioenergetics states, but did change neither caspases activities nor TNF-α levels in the frontal cortex of adult Wistar rats

Vitamin A and its derivatives, the retinoids, exert modulatory roles on central nervous system (CNS) function. However, the clinical use of vitamin A at moderate to high doses induces serious side effects. including dysfunctional brain metabolism and mood disorders. Then, we have investigated in this work the effects of vitamin A supplementation at 1000, 2500, 4500, or 9000 IU/kg/day for 28 days on redox and bioenergetics parameters in adult rat frontal cortex. Additionally, we have measured caspase-3 and caspase-8 activities to analyze whether vitamin A supplementation as retinol palmitate induces neuronal death in such brain area. The levels of the pro-inflammatory cytokine TNF-alpha were also quantified. We have found increased rates of O-2(-center dot) production and increased levels of markers of oxidative insult in frontal cortex and also in mitochondrial membranes. Superoxide dismutase (SOD) enzyme activity was increased, and catalase (CAT) enzyme activity did not change in this experimental model. Surprisingly, we observed increased mitochondrial electron transfer chain (METC) activity. Caspase-3 and caspase-8 activities and TNF-a levels did not change in this experimental model. Finally, vitamin A supplementation did not induce depression in adult rats after 28 days of treatment. However, exploration in the center of an open field was decreased and time spent in freezing behavior was increased in vitamin A treated rats. (C) 2008 Elsevier Ltd. All rights reserved.