回虫のNADH-フマル酸レダクターゼに対するビチオノールの阻害作用

概要

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To elucidate the mechanism of anthelmintic action of bithionol, the inhibitory effect of the drug on NADH-fumarate reductase (NADH-FR) of Ascaris lumbricoides suum was examined. NADH-FR, an enzyme of anaerobic carbohydrate metabolic pathway was solubilized from the mitochondria of the worm's muscle with deoxycholate, and then partially purified with the monoethanolamine-Sepharose 4B column chromatography. Rhodoquinone (RQ), which is required for the electron transfer from NADH to fumarate, 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 purified RQ and phosphatidylcholine. The IC_<50> value of bithionol for reconstituted NADH-FR was 18±2μM. The inhibition type was competitive to RQ. Bithionol inhibited at most 30% NADH-ferricyanide reductase, which did not require RQ, even at high concentration of 150μM. These results suggest that the pharmacological action of bithionol, a phenolic anthelmintic, depends on the inhibition of the electron transport system by the competition with RQ.
公益社団法人日本薬学会の論文
1993-09-25