Maeda Y, Takahashi M, Tashiro H, Akazawa F
Department of Pharmacy, Chugoku Rosai Hospital, Hiroshima, Japan.
J Pharmacobiodyn. 1989 May;12(5):272-80. doi: 10.1248/bpb1978.12.272.
From the standpoint of utilizing the distinctive feature of para-aminobenzoic acid (PABA) and the metabolism of intestinal bile acid, a conjugate of ursodeoxycholic acid with PABA (PABA-UDCA) was newly synthesized to study whether it can be a good material or not for the evaluation of the activity of intestinal bacterial growth. This compound was efficiently deconjugated in an incubation experiment with cholylglycine hydrolase resulting in the release of PABA. In a cultivation experiment, this compound was deconjugated by the same species of aerobic and anaerobic bacteria that deconjugated glycocholic acid. In an animal experiment, urinary excretions of PABA during 6 h following oral administration of 10 mg PABA-UDCA were determined. The control rat (n = 10) excreted 338.5 +/- 13.8 micrograms (mean +/- S.E.) of PABA. In contrast with this, the rats (n = 10) with intestinal antisepsis by the administration of polymyxin B and tinidazole excreted less PABA (14.0 +/- 2.5 micrograms; p less than 0.001), whereas the rats with intestinal bacterial overgrowth owing to the artificially made enteric blind loop excreted more PABA than the control rats did (673.6 +/- 70.2 micrograms; p less than 0.01). These observations indicate that this new compound is likely to offer a simple and rapid method for evaluation of intestinal bacterial growth.
从利用对氨基苯甲酸(PABA)的独特特性和肠道胆汁酸代谢的角度出发,新合成了熊去氧胆酸与PABA的共轭物(PABA-UDCA),以研究其是否可作为评估肠道细菌生长活性的良好材料。在与胆酰甘氨酸水解酶的孵育实验中,该化合物被有效地去共轭,导致PABA释放。在培养实验中,该化合物被与去共轭甘氨胆酸相同种类的需氧菌和厌氧菌去共轭。在动物实验中,测定了口服10mg PABA-UDCA后6小时内PABA的尿排泄量。对照大鼠(n = 10)排泄了338.5±13.8微克(平均值±标准误)的PABA。与此相反,通过给予多粘菌素B和替硝唑进行肠道防腐的大鼠(n = 10)排泄的PABA较少(14.0±2.5微克;p<0.001),而由于人工制造肠盲袢导致肠道细菌过度生长的大鼠排泄的PABA比对照大鼠多(673.6±70.2微克;p<0.01)。这些观察结果表明,这种新化合物可能提供一种简单快速的方法来评估肠道细菌生长。