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


OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Picard
C
C
Institut de Protection et de Sureté Nucléaire, Digestive Radiobiology Unit, Fontenay-aux-Roses Cedex, France.
Ksas
B
B
Griffiths
N M
NM
Fioramonti
J
J
D000818:Animals; D004573:Electrolytes; D005769:Gastrointestinal Motility / Q000187:drug effects* / Q000528:radiation effects; D017829:Granisetron / Q000494:pharmacology*; D007408:Intestinal Absorption / Q000187:drug effects* / Q000528:radiation effects; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects* / Q000503:physiopathology / Q000528:radiation effects; D008297:Male; D011833:Radiation Injuries, Experimental / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology*
D004573:Electrolytes; D017829:Granisetron; D012701:Serotonin; D012702:Serotonin Antagonists