Hirano T, Homma M, Oka K, Naito T, Hosaka K, Mitsuhashi H
Division of Clinical Pharmacology, Tokyo College of Pharmacy, Japan.
Life Sci. 1991;49(25):1871-8. doi: 10.1016/0024-3205(91)90287-l.
Diuretic properties of a synthetic lignan, 2,3-dibenzylbutane-1,4-diol (hattalin), and a naturally occurring arctigenin were examined in BALB/c male mice and Wistar male rats. Intra peritoneal administration of hattalin (50 mg/kg) in mice increased urine volume by 1.7-3.1 fold that of placebo-treated animals 40-260 min after administration (p less than 0.05 vs control). In contrast, 100 mg/kg of arctigenin had no effect on urine volume in mice. Hattalin (100 mg/kg), arctigenin (100 mg/kg), or furosemide (50 mg/kg) as a positive control was administered orally to rats, and accumulated urine volume was measured for up to 6-12 h. The urine volume of animals administered with hattalin showed 1.4-1.5 fold that of placebo-treated animals after 2-6 h of administration (P less than 0.05, n = 10). On the other hand, arctigenin showed no significant effect on urine volume for up to 12 h after administration (n = 8). The urine volume in animals administered with furosemide (n = 10) was 2.0-3.0 fold that of placebo-treated animals (P less than 0.01). Furosemide increased total Na+, K+, or Cl- excretion by 1.9, 1.8 or 2.2 fold, respectively, when compared with placebo-treated controls (P less than 0.01), whereas hattalin decreased Na+ excretion by 3.6 times (P less than 0.01), K+ excretion by 1.4 times (not significant), and Cl- excretion by 3.1 times (P less than 0.01). Serum Na+ and K+ levels did not change in both furosemide- and hattalin-administered rats, however, serum Cl- levels in these animals significantly decreased (P less than 0.01) when compared with controls. The results suggest that the diuretic property of hattalin is due to a novel mechanism which is different from that of furosemide or other diuretics modifying the ion-exchange at the uriniferous tubules.
在BALB/c雄性小鼠和Wistar雄性大鼠中检测了一种合成木脂素2,3 - 二苄基丁烷 - 1,4 - 二醇（哈他林）和天然存在的牛蒡子苷元的利尿特性。给小鼠腹腔注射哈他林（50毫克/千克）后40 - 260分钟，尿量增加至安慰剂处理动物的1.7 - 3.1倍（与对照组相比，p小于0.05）。相比之下，100毫克/千克的牛蒡子苷元对小鼠尿量没有影响。给大鼠口服哈他林（100毫克/千克）、牛蒡子苷元（100毫克/千克）或作为阳性对照的呋塞米（50毫克/千克），并测量长达6 - 12小时的累积尿量。给药2 - 6小时后，给予哈他林的动物尿量为安慰剂处理动物的1.4 - 1.5倍（P小于0.05，n = 10）。另一方面，牛蒡子苷元给药后长达12小时对尿量没有显著影响（n = 8）。给予呋塞米的动物（n = 10）尿量为安慰剂处理动物的2.0 - 3.0倍（P小于0.01）。与安慰剂处理的对照组相比，呋塞米使总Na⁺、K⁺或Cl⁻排泄分别增加1.9、1.8或2.2倍（P小于0.01），而哈他林使Na⁺排泄减少3.6倍（P小于0.01），K⁺排泄减少1.4倍（无显著性差异），Cl⁻排泄减少3.1倍（P小于0.01）。给予呋塞米和哈他林的大鼠血清Na⁺和K⁺水平均未改变，然而，与对照组相比，这些动物的血清Cl⁻水平显著降低（P小于0.01）。结果表明，哈他林的利尿特性归因于一种与呋塞米或其他改变肾小管离子交换的利尿剂不同的新机制。
