Schor N A, Huddleson R L, Kane G M, Lee G
Enzyme. 1983;30(4):244-51. doi: 10.1159/000469584.
The anticoagulants dicumarol, warfarin and diphenadione, are in vitro inhibitors of the enzyme reduced NAD(P)H dehydrogenase of rat liver. These chemicals were administered by intragastric gavage to determine whether the same inhibitory effects could be observed in Sprague-Dawley male rats. Doses of 2 and 10 mg/100 g body weight were used. Our results indicate that only dicumarol inhibited the enzyme, whereas warfarin did not produce a significant effect, and diphenadione at large doses produced an increase in the activity of the enzyme. Dicumarol was further tested to see if it would alter the activity of the enzyme in hyperplastic nodules and liver hepatomas. A similar inhibitory effect was found. The three strains of rats tested in this work have different levels of reduced NAD(P)H dehydrogenase activity. Thus, our results indicate that dicumarol is the only anticoagulant that inhibits in vivo the reduced NAD(P)H dehydrogenase of rat liver and liver neoplasms.
抗凝血剂双香豆醇、华法林和二苯茚二酮是大鼠肝脏中还原型NAD(P)H脱氢酶的体外抑制剂。通过灌胃给予这些化学物质,以确定在斯普拉格-道利雄性大鼠中是否能观察到相同的抑制作用。使用了2毫克/100克体重和10毫克/100克体重的剂量。我们的结果表明,只有双香豆醇抑制了该酶,而华法林没有产生显著影响,大剂量的二苯茚二酮则使该酶的活性增加。进一步测试了双香豆醇,看它是否会改变增生性结节和肝癌中该酶的活性。发现了类似的抑制作用。在这项工作中测试的三种大鼠品系具有不同水平的还原型NAD(P)H脱氢酶活性。因此,我们的结果表明,双香豆醇是唯一一种在体内抑制大鼠肝脏和肝脏肿瘤中还原型NAD(P)H脱氢酶的抗凝血剂。