lignans and 2-3-dibenzylbutane-1-4-diol

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.

Topics: Animals; Benzyl Compounds; Chlorides; Diuretics; Furans; Furosemide; Ion Exchange; Lignans; Male; Mice; Mice, Inbred BALB C; Natriuresis; Potassium; Rats; Rats, Inbred Strains; Sodium

The effect of each of twelve mammalian lignan derivatives on the growth of human mammary tumor ZR-75-1 cells was examined. At a concentration less than 10 micrograms/ml, tumor cell growth was inhibited from 18-68%. The effect of 2,3-dibenzylbutane-1,4-diol(hattalin) was found to be strongest, inhibiting growth by 50% at a concentration (EC50) of 2.1 micrograms/ml. Hattalin inhibited membrane Na+, K(+)-ATPase of canine kidney cortex. It also inhibited the ATPase of the plasma membrane fraction from both cultured cells and a section of human breast cancer tissue at a concentration ranging from 0.5 to 2.0 mM. However, only a few percent of membrane ATPase from either ZR-75-1 cells or breast carcinoma tissue was inhibited by 2.0 mM of ouabain, suggesting that the target ATPase of hattalin was other than ouabain-sensitive ATPase. The relative incorporation of [3H]thymidine per 1 x 10(5) cells into the acid-precipitable fraction of ZR-75-1 cells was not affected by 1-50 micrograms/ml of hattalin, while a marked decrease resulted from 1-10 micrograms/ml of 5-fluorouracil (5-FU). These results suggest that the suppressive effect of hattalin on tumor cell growth may not occur through inhibition of DNA synthesis but rather partly by inhibition of the plasma membrane ATPase other than Na+ and K(+)-dependent ones.

Topics: 4-Butyrolactone; Adenosine Triphosphatases; Animals; Benzyl Compounds; Breast Neoplasms; Butylene Glycols; Cell Division; Cell Line; Dogs; Dose-Response Relationship, Drug; Fluorouracil; Humans; Kidney Cortex; Lethal Dose 50; Lignans; Ouabain

We investigated the effect of 2,3-dibenzylbutane-1,4-diol (DBB), a mammalian lignan, on superoxide production and [Ca2+]i mobilization in human neutrophils. DBB did not generate superoxide production by itself, but enhanced the FMLP or A23187-induced superoxide production in a dose dependent manner. DBB did not influence the OAG-induced superoxide production. The priming effect of DBB was inhibited by W-7 or trifluoroperazine, but not by H-7 or staurosporine. And the priming effect of DBB was observed in the presence or absence of extracellular Ca2+. DBB enhanced the low dose FMLP-induced [Ca2+]i mobilization. These results suggest that the priming effect of DBB in human neutrophils may be caused by the activation of the calcium-calmodulin pathway but not the protein kinase pathway.

Topics: Alkaloids; Benzyl Compounds; Calcimycin; Calcium; Cell Compartmentation; Diglycerides; Humans; In Vitro Techniques; Lignans; Lignin; N-Formylmethionine Leucyl-Phenylalanine; Neutrophils; Protein Kinase C; Staurosporine; Sulfonamides; Superoxides; Trifluoperazine