Gastrointestinal Injury in Rats

The gastrointestinal injury potential of a candidate compound is studied in rats after oral administration. 

Every positive finding represents a serious safety issue for a candidate compound. 

Non-Steroidal Anti-Inflammatory Agents (NASID), like indomethacin and acetyl-salicylic acid (aspirin), induce gastric lesions in man and in experimental animals by inhibition of gastric cyclooxygenase (COX) resulting in less formation of prostacyclin, the predominant prostanoid produced in the gastric mucosa. 

After a 24 h starvation period groups of 8-10 rats weighing 150-200 g are used. The candidate compound is administered orally in 0.1 % Tween 80 solution. Six hours later, the rats are sacrificed in CO2 anesthesia and their stomachs and intestines are removed. The stomach and gastrointestinal tract are removed. The mucosa is examined with a stereomicroscope and examined and assessed in relation to an ulceration index. The number of ulcers is noted and the severity recorded with the following scores  

Indomethacin 20 mg/kg orally or aspirin 50-100 mg/kg can be used as standard for the induction of ulcers. 

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Bagchi, M. et al, Acute and chronic stress-induced oxidative gastrointestinal injury in rats, and the protective ability of a novel grape seed proanthocyanidin extract, Nutrition Res., 19,1189, 1999. 

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