Toxic oxygen metabolites reduce inactivation of prostaglandin E2 in isolated perfused rat lungs

The metabolic function of the lungs may be impaired in acute lung injuries. The present work examined the effect of toxic oxygen metabolites (TOM) on the pulmonary clearance of prostaglandin E2 (PGE2). Isolated rat lungs perfused with plasma were exposed to TOM, generated by xanthine oxidase (XO) and hypoxanthine (HX) in the perfusate. Inactivation of PGE2 was determined by superfusion bioassay technique. XO and HX (n = 6) reduced the inactivation of PGE2 from 78 +/- 4% (mean +/- SE) to 61 +/- 3%. This reduction was inhibited by the free radical scavengers superoxide dismutase and catalase, as well as by allopurinol, an inhibitor of XO. Neither hydrostatic lung edema nor perfusion per se decreased the inactivation of PGE2. Lungs pretreated with indomethacin still showed impaired PGE2 inactivation after exposure to XO and HX, indicating that a possible release of PGE2-like substances did not influence our findings. This study indicates that TOM may impair pulmonary metabolic function as shown by reduced inactivation of PGE2.