Effect of anti-inflammatory drugs on endotoxin-induced diarrhea in mice

Prostaglandins (PGs) increase the intestinal fluid to result in diarrhea. Some laxatives are known to exert their actions partially by stimulating the PGs biosynthesis. On the other hand, it is well documented that nonsteroidal anti-inflammatory drugs (NSAID) inhibit markedly the PGs biosynthesis. Since endotoxin (ETX) also produces diarrhea similarly in all species of experimental animals, we investigated the effect of various NSAID and steroidal anti-inflammatory drugs (SAID) on ETX-induced diarrhea in mice. ETX given p.o. did not produce diarrhea, but it could induce it after parenteral administration, especially intravenous injection. ALL NSAID and SAID tested inhibited ETX-induced diarrhea at dose levels similar to or lower than those commonly producing an acute anti-inflammatory effect. The anti-diarrheal effects were found in not only acidic NSAID, but also in basic NSAID and SAID which did not inhibited ultraviolet erythema, acute death induced by arachidonic acid injection and PGs biosynthesis. Therefore, this test using ETX-induced diarrhea in mice may be used as a new and desirable method for screening or evaluating anti-inflammatory drugs. The mechanism of diarrheogenic action of ETX is poorly understood, but may be attributed to inhibition of PGs biosynthesis besides other unknown actions.