Protocols to assess the gastrointestinal side effects resulting from inhibition of cyclo-oxygenase isoforms.
A prevalent unwanted action of cyclo-oxygenase (COX) inhibitors, as exemplified by the non-steroidal anti-inflammatory drugs (NSAIDs), is their potential to produce gastrointestinal side effects in clinical use. The injury provoked by such agents includes rapid superficial disruption to the surface layer of the gastric mucosa, the production of acute gastric erosions in the corpus region and the formation of ulcers in the antral region of the stomach. The small intestine is also adversely affected, with a developing enteropathy over a more protracted period that causes lesions and inflammation in the gut. From experimental work, the interactive mechanisms of such damage in the stomach differ distinctly from those that underlie the intestinal injury, yet the damage in both regions involves the inhibition of both COX-1 and COX-2 isoforms. This chapter outlines the in vivo methods that can be used to identify the potential for novel NSAIDs and selective COX-inhibitors to produce acute gastric corpus lesions and more-chronic antral ulcers in the rat, as well as causing small intestinal enteropathy. Such methods can also be utilized to evaluate the ability of novel agents to prevent the gastrointestinal injury provoked by NSAIDs or COX-inhibitors.
Whittle
Brendan J R
BJ
St. Bart&s and the London School of Medicine and Dentistry, William Harvey Research Institute, Queen Mary University of London, London, UK. b.j.whittle@qmul.ac.uk
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects*; D005753:Gastric Mucosa / Q000187:drug effects; D041981:Gastrointestinal Tract / Q000187:drug effects*; D007421:Intestine, Small / Q000187:drug effects; D008297:Male; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000139:chemically induced
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D011451:Prostaglandin-Endoperoxide Synthases