Ikuma K, Makimura M, Murakoshi Y
College of Pharmacy, Nihon University, Funabashi, Japan.
Yakugaku Zasshi. 1993 Sep;113(9):663-9. doi: 10.1248/yakushi1947.113.9_663.
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 IC50 value of bithionol for reconstituted NADH-FR was 18 +/- 2 microM. 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 150 microM. 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.
为阐明硫双二氯酚的驱虫作用机制，研究了该药物对猪蛔虫NADH-延胡索酸还原酶（NADH-FR）的抑制作用。NADH-FR是无氧碳水化合物代谢途径中的一种酶，用脱氧胆酸盐从虫体肌肉线粒体中溶解出来，然后用单乙醇胺-琼脂糖4B柱色谱法进行部分纯化。从酶蛋白和磷脂中分离出了NADH向延胡索酸电子传递所需的玫红醌（RQ）。尽管从上述柱中洗脱的酶蛋白组分未显示NADH-FR活性，但通过添加纯化的RQ和磷脂酰胆碱可使该酶重新激活。硫双二氯酚对重组NADH-FR的IC50值为18±2微摩尔。抑制类型对RQ具有竞争性。即使在150微摩尔的高浓度下，硫双二氯酚对不需要RQ的NADH-铁氰化物还原酶的抑制作用最多为30%。这些结果表明，酚类驱虫药硫双二氯酚的药理作用取决于通过与RQ竞争对电子传递系统的抑制。
