van Gorkom B A P, van der Meer R, Boersma-van Ek W, Termont D S M L, de Vries E G E, Kleibeuker J H
Dept of Gastroenterology, University Hospital, Groningen, The Netherlands.
Scand J Gastroenterol. 2002 Aug;37(8):965-71. doi: 10.1080/003655202760230955.
Ursodeoxycholic acid (UDCA) has been shown to affect membrane-damaging effects of bile acids in vitro and fecal bile acid composition in rats. This study evaluates the effect of UDCA on fecal bile acid composition and on cytolytic activity of fecal water in man to clarify the potential chemopreventive role of UDCA for colorectal cancer.
In this placebo-controlled crossover intervention trial, the effect of 900 mg/day UDCA orally in 15 healthy volunteers was studied. At the end of each 4-week period, 72 h feces were collected. Total and individual bile acids in feces were determined by gas chromatography and soluble bile acids were analyzed by high-performance liquid chromatography. Cytolytic activity of fecal water was measured using an erythrocyte lysis assay.
In feces, the percentages of primary bile acids-cholic acid (CA) and chenodeoxycholic acid (CDCA)-and of secondary bile acid-deoxycholic acid (DCA) - decreased after supplementation with UDCA, whereas those of UDCA and LCA increased from 2.7 +/- 0.4% to 23.7 +/- 2.6%, P < 0.0001 and from 26.2 +/- 1.2% to 49.4 +/- 1.8%, P < 0.0001 respectively. The concentrations of these two bile acids in fecal water also increased after UDCA administration from 7.8 +/- 1.9 micromol/l to 47.0 +/- 6.7 micromol/l (UDCA), P < 0.0001 and from 2.5 +/- 0.6 micromol/l to 18.3 +/- 4.1 micromol/l (LCA), P < 0.002, respectively. Cytolytic activity of fecal water was not affected by UDCA.
These results do not support a protective effect of UDCA supplementation against colorectal cancer in man.
熊去氧胆酸(UDCA)已被证明在体外可影响胆汁酸的膜损伤作用,并改变大鼠粪便中胆汁酸的组成。本研究旨在评估UDCA对人体粪便胆汁酸组成及粪便水细胞溶解活性的影响,以阐明UDCA对结直肠癌的潜在化学预防作用。
在这项安慰剂对照的交叉干预试验中,研究了15名健康志愿者口服900毫克/天UDCA的效果。在每个4周周期结束时,收集72小时的粪便。粪便中的总胆汁酸和各胆汁酸通过气相色谱法测定,可溶性胆汁酸通过高效液相色谱法分析。使用红细胞裂解试验测量粪便水的细胞溶解活性。
在粪便中,补充UDCA后,初级胆汁酸——胆酸(CA)和鹅去氧胆酸(CDCA)以及次级胆汁酸——脱氧胆酸(DCA)的百分比降低,而UDCA和石胆酸(LCA)的百分比分别从2.7±0.4%增加到23.7±2.6%,P<0.0001,从26.2±1.2%增加到49.4±1.8%,P<0.0001。服用UDCA后,粪便水中这两种胆汁酸的浓度也分别从7.8±1.9微摩尔/升增加到47.0±6.7微摩尔/升(UDCA),P<0.0001,从2.5±0.6微摩尔/升增加到18.3±4.1微摩尔/升(LCA),P<0.002。粪便水的细胞溶解活性不受UDCA影响。
这些结果不支持补充UDCA对人类结直肠癌有保护作用。