INHIBITORY EFFECT OF BITHIONOL ON NADH-FU MARATE REDUCTASE IN ASCARIDES

To elucidate the mechanism of anthelmintic action of bithionol, the in hibitory effect of the drug on NADH-fumarate reductase (NADH-FR) of As caris lumbricoides suum was examined. NADH-FR, an enzyme of anaerobic carbohydrate metabolic pathway was solubilized from the mitochondria o f the worm's muscle with deoxycholate, and then partially purified wit h the monoethanolamine-Sepharose 4B column chromatography. Rhodoquinon e (RQ), which is required for the electron transfer from NADH to fumar ate, was separated from the enzyme protein and phospholipids. Although the enzyme protein fraction eluted from the above column did not show NADH-FR activity, this enzyme was reactivated by the addition of puri fied RQ and phosphatidylcholine. The IC50 value of bithionol for recon stituted NADH-FR was 18+/-2 mum. The inhibition type was competitive t o RQ. Bithionol inhibited at most 30% NADH-ferricyanide reductase, whi ch did not require RQ, even at high concentration of 150 mum. These re sults suggest that the pharmacological action of bithionol, a phenolic anthelmintic, depends on the inhibition of the electron transport sys tem by the competition wit RQ.