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Evidence-Based Complementary and Alternative Medicine
Volume 2011, Article ID 315858, 8 pages
Research Article

Cattle Bile Aggravates Diclofenac Sodium-Induced Small Intestinal Injury in Mice

Division of Clinical Application, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan

Received 17 November 2010; Revised 17 February 2011; Accepted 18 February 2011

Copyright © 2011 Hironori Ishikawa and Shiro Watanabe. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Cattle bile (CB) has long been used in Japan as an ingredient of digestive medicines. Bile acids are major chemical constituents of CB, and CB ingestion is assumed to affect small intestinal injury induced by nonsteroidal anti-inflammatory drugs (NSAIDs). Mice were fed a diet supplemented with or without CB for 7 days and treated with diclofenac sodium (DIF) to induce small intestinal injury. Lesion formation was enhanced, and PGE2 content and COX expression levels were elevated in the small intestine of DIF-treated mice fed the CB diet compared with those fed the control diet. The administration of a reconstituted mixture of bile acids found in CB enhanced lesion formation in DIF-treated mice. CB administration elevated the contents of CB-derived bile acids in the small intestine, some of which exhibited a high cytotoxicity to cultured intestinal epithelial cells. These results suggest that the elevated levels of CB-derived cytotoxic bile acids in the small intestine contribute to the aggravation of DIF-induced small intestinal injury. The use of CB may be limited during the therapy of inflammatory diseases with NSAIDs.