Effects of misoprostol on delayed ulcer healing induced by aspirin

Clinical studies have suggested that treatment with the prostaglandin E1 analog, misoprostol, leads to significant healing of ulcers in patients taking regular nonsteroidal antiinflammatory therapy. This study aimed to investigate mechanisms involved in this healing using a rat model. Gastric ulcers were induced by application of acetic acid using a standard technique. Rats were treated with 200 mg/kg aspirin, 100 micrograms/kg misoprostol, a combination of both treatments, or methylcellulose vehicle for up to two weeks, starting two days after ulcer induction. Ulcers were assessed by macroscopic measurements of area and by quantitative histological measurements. Aspirin delayed ulcer healing compared with controls, while misoprostol significantly reversed this effect. Quantitative histology revealed that misoprostol cotreatment significantly increased mucosal regeneration compared with aspirin treatment alone. However, misoprostol did not reverse the effects of aspirin on an index of wound contraction. We conclude that treatment with misoprostol significantly reverses the delayed healing effect of aspirin, and this may occur via an effect on epithelial regeneration.