Inhibition of tissue damage by the arachidonate lipoxygenase inhibitor BW755C.

Abstract

The effects of 3 anti-inflammatory drugs, which interefere with arachidonic acid transformation by 3 different enzymes, were compared by using a simple model of tissue damage and foreign body rejection. In groups of control rats, s.c. implanted polyester sponges were rejected after a mean of 12 days. Indomethacin, which selectively inhibits prostaglandin synthesis, did not significantly change time to rejection but BW755C (3-amino-1-[m-(trifluoromethyl)phenyl]-2-pyrazoline), which is a dual inhibitor of prostaglandin and leukotriene synthesis, prolonged time to rejection to a mean of 22 days. The anti-inflammatory steroid dexamethasone, which reduces arachidionic acid metabolism by stimulating the formation of a phospholipase inhibitor, prolonged time to sponge rejection as BW755C did. Treatment with BW755C or dexamethasone was also accompanied by a reduction in total leukocyte numbers in inflammatory exudates collected at 1-14 days while indomethacin increased leukocyte migration on days 1 and 2 and had no effect at later times. Apparently, the inhibition of the leukotriene-forming lipoxygenase suppresses leukocyte activation, and this leads to a reduced rate of tissue damage in experimental inflammation.