Cisplatin impairs fluid and electrolyte absorption in ratsmall intestine: a role for 5-hydroxytryptamine

Background—Theantineoplastic drug cisplatin has been widely used for the treatment ofcancer in humans but its use has been limited by vomiting anddiarrhoea. Cisplatin releases 5-hydroxytryptamine into the gutwhich is thought to be the major mediator of cisplatin induced vomiting.
Aim—To determinewhether cisplatin affects fluid and electrolyte transport in ratjejunum and whether this change can be modulated by the5-hydroxytryptamine₃ receptor antagonist, ondansetron.
Methods—Jejunalperfusion in rats in vivo was performed one hour after intraperitonealcisplatin (5 and 10 mg/kg) administration. The effect of pretreatmentwith subcutaneous ondansetron 300 µg/kg was investigated.
Results—Median netfluid absorption after cisplatin 10 mg/kg (67 µl/min/g dry intestinalweight (interquartile range 46 to 100); n = 15) was reduced comparedwith controls (120 (107to 151) µl/min/g; n = 13; p<0.001).Ondansetron reversed the impairment of jejunal fluid absorptionproduced by cisplatin to normal (161(130 to 176) µl/min/g; n = 11;p<0.001). Electrolyte movement paralleled fluid movement. Jejunalhistological examination of sections from cisplatin treated animalsshowed villus damage, which was not prevented by pretreatment with ondansetron.
Conclusion—Thesefindings suggest that diarrhoea during cisplatin therapy may be due toaltered fluid transport in the small bowel. The reversal of fluidtransport to normal in the presence of a5-hydroxytryptamine₃ receptor antagonist suggests that5-hydroxytryptamine is a local mediator in the small intestine.