THE ROLE OF PROSTAGLANDIN-H SYNTHASE IN 3-METHYLINDOLE-INDUCED PNEUMOTOXICITY IN GOAT

1. Aspirin and indomethacin were used to investigate the role of prostaglandin H synthase (PHS) system in 3-methylindole (3MI)-induced pneumotoxicity. 2. A functional test was developed to detect the inhibitory effect of oral doses of aspirin and indomethacin on PHS activity based on thromboxane B2 (TXB2) production from thrombin-stimulated platelets in whole blood. 3. Goats which received oral doses of aspirin or indomethacin before administration of 3MI (0.1 g 3MI/kg body wt) showed a reduced severity in clinical signs and pathological lesions in the lung than those that received 3MI alone. 4. There was no difference in the severity of the disease between the control and the aspirin-treated animals if aspirin was given after 3MI administration. 5. The protective effect of inhibitors when administered before, but not after, 3MI dosing suggests it is the inhibition of PHS activity in activation of 3MI, not in production of prostanoids which prevented the disease process.