Ketotifen ameliorates development of fibrosis in alkali burns of the esophagus.

An experimental study was performed to investigate the efficacy of ketotifen, which is a mast cell stabilizer and histamine H(1)-receptor antagonist, on the prevention of stricture development after esophageal caustic injuries in the rat. Caustic esophageal burn was created by applying 37.5% NaOH to the distal esophagus. Forty rats were divided into four equal groups. Group A (sham) animals were uninjured. Group B rats were injured but untreated. Group C rats were injured and received ketotifen (1 mg/kg/day) via the oral route. Group D rats were injured and received ketotifen (1 mg/kg/day) via the intraperitoneal route. Efficacy of the treatment was assessed on day 28 by measuring the stenosis index and histopathologic damage score and biochemically by determining tissue hydroxyproline content. The stenosis index in group B (0.93+/-0.22) was significantly increased compared with group A (0.39+/-0.06, p <0.05), group C (0.42+/-0.09, p <0.05), and group D (0.35+/-0.07, p <0.05). The hydroxyproline level ( micro g/mg wet tissue) was significantly increased in group B (1.31+/-0.08, p <0.05) compared with group A (0.69+/-0.16, p <0.05), group C (1.06+/-0.16, p <0.05), and group D (0.95+/-0.12, p <0.05). In group B the histopathologic damage score was significantly higher than in groups C ( p<0.05) and D ( p<0.05). There was no significant difference between group C and group D in terms of all parameters evaluated. Treatment with ketotifen decreased tissue hydroxyproline levels, histological damage, and the stenosis index. We conclude that ketotifen has a preventive effect in the development of fibrosis in an experimental model of corrosive esophagitis in rats.