Effect of antioxidant therapy on cyclooxygenase-derived eicosanoid release during intestinal ischemia-reperfusion.
Conflicting data have been reported on the relationship between reactive oxygen intermediates and the formation of oxygenase-derived eicosanoids. Plasma levels of prostacyclin (PGI2, measured as the stable metabolite 6-keto-PGF1 alpha) and thromboxane A2 (TxA2, measured as TxB2) in the effluent blood of a canine ileal segment were determined following 1 or 2 h of ischemia. The synthesis of both eicosanoids was significantly stimulated during reperfusion, but extension of the ischemic interval from 60 to 120 min was not followed by a further increase. The role of oxidants potentially involved in the process was investigated by using materials that inactivate the xanthine-oxidase-generated intermediates. Previous studies on the same in vivo animal model had demonstrated the effectiveness of antioxidant therapy in reducing the postischemic histamine release. There was no significant alteration in the amount of eicosanoids synthesized following oral allopurinol, catalase, dimethylsulfoxide, mannitol or desferrioxamine treatment. Intravenously administered allopurinol, however, significantly elevated the postischemic 6-keto-PGF1 alpha/TxB2 ratio. The results suggest that these antioxidants at doses inhibitory to histamine liberation are not effective in influencing the postischemic eicosanoid release. Intravenously administered allopurinol could exert a potentially beneficial effect through a mechanism other than the blockade of xanthine oxidase.
Boros
M
M
Institute of Experimental Surgery, Szent-Györgyi Albert Medical University, Szeged, Hungary.
Bakó
L
L
Nagy
S
S
D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D004285:Dogs; D011464:Epoprostenol / Q000378:metabolism*; D005260:Female; D007422:Intestines / Q000098:blood supply*; D007511:Ischemia / Q000378:metabolism; D008297:Male; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D015427:Reperfusion Injury / Q000188:drug therapy*; D013928:Thromboxane A2 / Q000378:metabolism*
D000975:Antioxidants; D013928:Thromboxane A2; D000493:Allopurinol; D011464:Epoprostenol; D011451:Prostaglandin-Endoperoxide Synthases