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 LTC₄D₄E₄were determined by radioimmunoassay. PGE₂in 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 LTC₄D₄E₄between the two groups. Our study shows that hypoxia shifts the arachidonic acid metabolism toward enhanced lipoxygenase activity with a resultant increase in LTB₄levels and a concomitant decrease in cyclooxygenase activity with reduced PGE₂levels 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 cytoprotec-tion.