EICOSANOIDS IN HYPOXIC INSULT TO NEONATAL RABBIT BOWEL

Eicosanoids, derivatives of arachidonic acid, play a role in several inflammatory diseases of the bowel. To determine whether prostaglandin E2 (PGE2), leukotriene B4 (LTB4), and leukotriene C4D4E4 (LTC4D4E4), have a role in hypoxic insult to the intestine, we examined the levels of these mediators in a hypoxic neonatal rabbit model. One group of animals underwent hypoxic insult postnatally, the second group did not undergo hypoxia and served as a control. The levels of PGE2, LTB4, and LTC4D4E4 were determined by radioimmunoassay. PGE2 in the hypoxic group was 1,779 +/- 142 pg/mg protein (mean +/- SD) as opposed to 2,380 +/- 197 pg/mg protein in the control group (p < 0.02). LTB4 level was 5,446 +/- 3,492 pg/mg protein in the hypoxic rabbits and 3,362 +/- 2,570 pg/mg protein in the control group (p < 0.03). There was no statistically significant difference in the level of LTC4D4E4 between the two groups. Our study shows that hypoxia shifts the arachidonic acid metabolism toward enhanced lipoxygenase activity with a resultant increase in LTB4 levels and a concomitant decrease in cyclooxygenase activity with reduced PGE2 levels in the bowel. The shift in the balance between these eicosanoids may play a role in the pathogenesis of ischemic-hypoxic bowel diseases by enhancing the inflammatory response in the intestine, and simultaneously, diminishing cytoprotection.