Effect of granisetron on radiation-induced alterations of colonic motility and fluid absorption in rats.

Abstract

Radiation-induced diarrhoea is attributed to both mucosal injury and alterations of intestinal motility. Previous reports have indicated that 5-hydroxytryptamine is released following irradiation, which may contribute to these changes. To investigate the effects of granisetron (5-hydroxytryptamine type-3 receptor antagonist) on colonic motility, fluid absorption and 5-hydroxytryptamine colonic content following abdominal irradiation (10 Gy) in rats. In vivo measurements of motility and fluid absorption in the proximal and distal colon, respectively, diarrhoea score and 5-hydroxytryptamine tissue levels were performed 3 and 7 days after abdominal irradiation. The effects of post-irradiation granisetron (0.3 mg/kg subcutaneously) were also evaluated. Colonic motility and fluid/Na(+) absorption were reduced 3 and 7 days after irradiation. All rats developed diarrhoea (3 days) concomitant with increased colonic mucosal 5-hydroxytryptamine levels. Granisetron prevented diarrhoea, attenuated decreased colonic motility and reduced 5-hydroxytryptamine levels on day 3, although fluid absorption was only slightly improved. On day 7, colonic motility and fluid/Na(+) absorption were restored in granisetron-dosed animals. These results indicate that radiation-induced diarrhoea involves alterations of both colonic motility and fluid/Na(+) absorption. 5-Hydroxytryptamine could be one of the mediators implicated in these alterations, as post-irradiation dosage with a 5-hydroxytryptamine type-3 receptor antagonist improved colonic motility and prevented diarrhoea on day 3.