Enrichment of the more hydrophilic bile acid ursodeoxycholic acid in the fecal water-soluble fraction after feeding to rats with colon polyps

• Published in: Cancer research (Chicago, Ill.) Vol. 58; no. 8; pp. 1684 - 1687
• Main Authors: BATTA, A. K, SALEN, G, HOLUBEC, H, BRASITUS, T. A, ALBERTS, D, EARNEST, D. L
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.04.1998
• Subjects: Animal tumors. Experimental tumors; Animals; Azoxymethane - pharmacology; Bile Acids and Salts - analysis; Bile Acids and Salts - pharmacology; Biological and medical sciences; Cholic Acid; Cholic Acids - metabolism; Cholic Acids - pharmacology; Colonic Polyps - drug therapy; Deoxycholic Acid - metabolism; Experimental digestive system and abdominal tumors; Feces - chemistry; Lithocholic Acid - metabolism; Male; Medical sciences; Rats; Rats, Inbred F344; Retrospective Studies; Tumors; Ursodeoxycholic Acid - metabolism; Ursodeoxycholic Acid - pharmacology; Rat; Rodentia; Oral administration; Malignant tumor; Anticarcinogen; Carcinogenesis; Ursodeoxycholic acid; Colonic disease; Prevention; Vertebrata; Mammalia; Cytoprotector; Bile acid; Animal; Digestive diseases; Intestinal disease; Hydrophilic compound; Colon; Feces
• ISSN: 0008-5472; 1538-7445

We recently showed that feeding the cytoprotective bile acid ursodeoxycholic acid (UDCA) to rats resulted in significant reduction in polyps and especially cancers, both in number and size (D. L. Earnest et al., Cancer Res., 54: 5071-5074, 1994). Because fecal secondary bile acids [particularly deoxycholic acid (DCA)] are considered to promote formation of colon adenomas and cancer, we have now attempted to find a relationship between polyp reduction and fecal secondary bile acids after feeding UDCA to these rats. We examined the fecal bile acids in rats with polyps and compared them with fecal bile acids in control rats and also determined the bile acid composition in fecal aqueous phase, which is in direct contact with the colon epithelium and may be physiologically more active. Treatment with azoxymethane did not significantly alter fecal bile acid composition in the rats. Cholic acid feeding resulted in greatly increased proportions of DCA (82% of total bile acids versus 18% in control rats). On the other hand, UDCA feeding significantly reduced the proportion of fecal DCA (2% in control rats fed UDCA and 3% in rats also treated with azoxymethane). In control rats, 96% of the bile acids were present in the water-insoluble fraction and 4% in the water-soluble fraction. The major insoluble bile acids included DCA and hyodeoxycholic acid (73% of total bile acids). In contrast, the muricholic acids were concentrated in the soluble fraction (37%). When 0.4% UDCA was added to the diet, lithocholic acid increased in the insoluble fraction (40 versus 1%), but the hydrophilic UDCA and muricholic acids were enriched in the water-soluble fraction (37 and 43%, respectively). Thus, the hydrophobic bile acids were distributed predominantly in the water-insoluble fraction, whereas the hydrophilic bile acids were distributed preferentially in the water-soluble fraction. These data suggest that UDCA may prevent colon tumors and polyps by countering the toxic effect of DCA and enhancing the possible cytoprotective effects of UDCA and muricholic acids in the water-soluble fraction in the feces of rat.