Evaluation of a bovine colostral preparation as treatment for gastrointestinal injury

Growth factors play an important role in repair of the injured gut as well as maintaining gut homeostasis. De-fatted bovine colostrum is a health food supplement containing significant amounts of growth factors. Thus, derivatives from bovine colostrum might be an inexpensive treatment for gut injury (e.g. inflammatory bowel disease (IBD)), and as a prophylactic against injurious effects of drugs such as non-steroidal anti-inflammatory drugs (NSAIDs).;The studies presented in this thesis were devised to test the effects of a commercially-available bovine colostral preparation on wound healing and proliferation in vitro, and in an animal model of IBD. The effect of TGF2, a major colostral growth factor, on NSAID-induced murine small intestinal injury was also tested. Finally, the effects of bovine colostral preparation on intracellular signalling leading to stimulated DNA synthesis was investigated.;Bovine colostral preparation stimulated DNA synthesis and proliferation in cultured intestinal epithelial cells, and also stimulated epithelial migration following wounding. Motogenic effects were independent of proliferation. Colostral components greater than 30 kDa in weight were mostly responsible for these effects.;Motogenic, but not mitogenic, components were resistant to transient acidification, such as might be encountered in the stomach. Transient acidification liberated active TGF. TGF2, the major colostral TGF isoform, was prophylactic against murine small intestinal NSAID-induced damage.;Oral bovine colostral preparations stimulated healing of chemically-induced colitis in rats, but had no effect on the induction of colitis. Topical application of the colostral preparation by enema was ineffective.;Inhibition of growth factor receptors inhibited some, but not all, proliferative activity in colostral preparation. Some effects of colostral preparation were due to activation of the EGF receptor despite the absence of EGF in the preparation.;In conclusion, bovine colostral preparation might act as an orally-active prophylactic and healing agent for a variety of gastrointestinal injuries.