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Mesalazine microgranules (Pentasa) were developed as a drug for idiopathic inflammatory bowel diseases such as ulcerative colitis and Crohn's disease. In this study, we examined the effect of mesalazine on radical scavenging, lipid peroxidation and the formation of LTB4. Mesalazine reduced the free radical 1,1-diphenyl-2-picrylhydrazyl with an IC50 value of 9.5 microM. It scavenged hydrogen peroxide and hypochlorite (IC50: 0.7 microM and 37.0 microM, respectively), but had no effect on superoxide. Lipid peroxidation in rat liver microsomes was inhibited by mesalazine (IC50: 12.6 microM). Mesalazine significantly inhibited (P &lt; 0.01) gastric mucosal lipid peroxidation induced by ischemia and reperfusion in rats at a dose of 50 mg/kg, p.o. Mesalazine also inhibited the formation of LTB4 in rat peritoneal neutrophils (IC50: 44.9 microM). N-Acetyl-mesalazine, the metabolite of mesalazine, had no effect on radical scavenging and lipid peroxidation. Only a high concentration (1 mM) of the metabolite inhibited the formation of LTB4. These studies suggest that mesalazine inhibits cell injury in the inflamed mucosa by scavenging reactive oxygen metabolites and prevents the invasion of neutrophils by inhibition of LTB4 formation.

Effect of mesalazine, an agent for the treatment of idiopathic inflammatory bowel disease, on reactive oxygen metabolites and LTB4 formation.