Arachidonic acid supplementation dose-dependently reverses the effects of a butter-enriched diet in rats

Male Sprague Dawley rats were fed a butter-enriched diet (50% fat) for 2 weeks which was supplemented orally with 9, 18, 36, or 72 mg/day of ethyl arachidonate for a further 2 weeks. The control group of animals were fed a 5% fat diet for 4 weeks. Aortic prostacyclin (PGI₂) production, platelet aggregation and thromboxane A₂ (TXA₂) production and plasma and aortic phospholipid (PL) fatty acids were measured. 50% butter-feeding resulted in a significant reduction in aortic PGI₂ production and collagen-induced platelet aggregation and TXA₂ production. These changes were accompanied by a reduction in plasma and aortic PL arachidonic acid levels and an increase in eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), 5,8,11-eicosatrienoic acid (ETA) and dihomo-gamma-linolenic acid (DGLA). These changes in prostanoid production, platelet aggregation and PL fatty acid composition were dose-dependently reversed by the daily oral administration of ethyl arachidonate (9, 18, 36, or 72 mg). The threshold dose being as little as 9 mg of ethyl arachidonate/rat/day for reversal of PL fatty acid composition, collagen-induced platelet aggregation and TXA₂ production, and 18 mg of ethyl arachidonate/rat/day for reversal of aortic PGI₂ production. Full reversal was seen generally with 36 or 72 mg of ethyl arachidonate/rat/day. The data highlight the responsiveness of tissue eicosanoid production to small quantities (ppm) of dietary eicosanoid precursors.