Ethyl docosahexaenoate-associated decrease in fetal brain lipid peroxide production is mediated by activation of prostanoid and nitric oxide pathways

Previously we have shown that intraamniotic administration of ethyl docosah exaenoate (Et-DHA) to pregnant rats resulted in decreased lipid peroxidatio n in the fetal brain, under a variety of conditions (S. Glozman, P. Green, E. Yavin, J. Neurochem. 70 (1998) 2482-2491). In the present study we exami ne the potential mechanisms to explain this effect. This was done by a phar macological approach, utilizing brain slice preparations from Et-DHA treate d or control rats in the presence of various agents and examining the forma tion of products in the tissue slices or incubation medium. Et-DHA treated brains produced 2-3-foId more prostanoids (PN) than control brains, indicat ing cyclooxygenase (COX) activation. Indomethacin at 50 muM inhibited PN fo rmation and also abolished Et-DHA induced decrease in lipid peroxides, as e vident by the levels of thiobarbituric acid reactive substances (TBARS) rel eased in the medium. The phospholipase A(2) inhibitors quinacrine and p-bro mophenacyl bromide added at 0.1 mM concentration each to either slices from controls or Et-DHA treated fetal brains, decreased TBARS production. Et-DH A treated brains released 2.2-fold more nitric oxide (NO) than control brai ns and NO synthase (NOS) inhibitors abolished this effect. Increasing the c oncentration of NO by the addition of an NO donor greatly decreased the con centration of the TEARS in the medium. These results suggest that at least some of the effect of Et-DKA on decreased lipid peroxidation may be explain ed by a shift of oxygen species utilization via enzymaticatlly regulated, t herefore metabolically controlled, COX and NOS activities. (C) 2001 Elsevie r Science B.V. All rights reserved.