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Influence of Dietary Fat, Vitamin E, Ethoxyquin and Indomethacin on the Synthesis of Prostaglandin E₂ in Brain Regions of Mice¹

U.S. Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111

The regional brain synthesis of prostaglandin E₂ (PGE₂) of rats varies with age and dietary vitamin E. We investigated ex-vivo synthesis of PGE₂ in brain regions of 24-mo-old male C57BL/6Nia mice. Mice were fed semipurified diets containing 1) 5% by weight of vitamin E-stripped corn oil, nonhydrogenated coconut oil or fish oil, or 2) 3.8% lard + 1.2% stripped corn oil (control), each supplemented with 30 or 500 mg of vitamin E per kg for 6 wk. In addition, two groups of mice were fed control diets containing 2500 mg of ethoxyquin/kg or 1 mg of indomethacin/(kg-day). Mice fed fish oil had lower (P < 0.01) plasma -tocopherol than those fed coconut oil. Vitamin E supplementation had no effect on the concentration of -tocopherol in most brain regions. The rank order of PGE₂ synthesis among all groups was cerebrum = cerebellum > midbrain > brainstem. Vitamin E supplementation tended to reduce brain PGE₂ synthesis. Fat with 30 mg/kg of vitamin E had no effect on brain PGE₂ synthesis. Mice fed fish oil had significantly lower PGE₂ compared with mice fed coconut oil when they received 500 mg/kg of vitamin E in their diet. In the brainstem, fish oil significantly reduced PGE₂ relative to mice fed corn oil. Ethoxyquin lowered plasma -tocopherol by 42% and reduced the PGE₂ synthesis in brain regions, and indomethacin reduced it by 50%. Thus, ethoxyquin and indomethacin significantly reduced the brain's regional capacity for PGE₂ synthesis, whereas vitamin E was not effective for the period tested. The reduction of PGE₂ synthesis in the brain with fish oil feeding in this study was not as notable as reported for other tissues unless combined with high-dose vitamin E supplementation.

KEY WORDS: • dietary fat • vitamin E • ethoxyquin • prostaglandin E₂ • brain • mice

¹ Supported by National Institute on Aging Grant No. 1R23AG045791-01 and U.S. Department of Agriculture Contract No. 53-3K06-5-10.

Manuscript received 9 May 1990. Revision accepted 9 October 1990.