The effect of dietary supplementation with n-3 polyunsaturated fatty acids on the generation of platelet-activating factor and leukotriene B4 in hypoxic-ischemic brain in young mice.

Platelet-activating factor (PAF), leukotriene B(4) (LTB(4)) and other cytokines have been indicated to be responsible for the neuronal damage in hypoxic-ischemic brain. Diets in omega-3 (n-3) fatty acids appear to have an antiinflammatory effect, which is thought to be due to decrease in active prostaglandins and leukotrienes production after incorporation of these fatty acids into cell membrane phospholipids. We investigated the effect of dietary supplementation with n-3 fatty acids on endogenous PAF and LTB(4) biosynthesis in hypoxic-ischemic brain of young mice. Young mice were randomly divided into four groups: Group 1 mice were fed standard chow (n-3 polyunsaturated fatty acids free); Group 2 and Group 3 mice were given standard diet supplemented with 10% by weight of fish oil, as source of n-3 polyunsaturated fatty acids, for 3 and 6 weeks, respectively. Group 4 mice served as control. We injured the right cerebral hemisphere of young mice by ligating the right common carotid artery and exposing the mice to 8% oxygen for 60 min. Approximately 10-fold increase in PAF concentration was determined in hypoxic-ischemic brain tissue of Group 1 mice. Tissue concentration of PAF showed a profound decline in Group 3 mice compared to Groups 1 and 2 (P<0.01, P<0.05, respectively). LTB(4) was also significantly elevated in the brain of Group 1 mice when compared to the brain of control mice (P<0.001). A striking decline was observed in the concentration of LTB(4) in both Group 2 and Group 3 mice compared to Group 1 mice (P<0.05, P<0.01, respectively). The present study shows that n-3 fatty-acid-enriched diet inhibits endogenous PAF and LTB(4) generation in hypoxic-ischemic brain tissue; however it demonstrates that 6 weeks of dietary supplementation with n-3 fatty acids results in a significant decrease in tissue level of PAF in the brain.