Relevance of Irinotecan Hydrochloride-Induced Diarrhea to the Level of Prostaglandin E_2 and Water Absorption of Large Intestine in Rats

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For characterization of the mechanism(s) of severe diarrhea due to the anticancer agent, irinotecan hydrochloride (CPT-11), examination was made of the relation of CPT 11 -related diarrhea to colonic prostaglandin E<SUB>2</SUB> (PGE<SUB>2</SUB>) and water absorption in rats. Acute diarrheal symptoms were observed within 1 hr after the administration of CPT-11 to rats, with increased PGE<SUB>2</SUB> and decreased water absorption in the colon. Treatment with atropine at 1 mg/kg, s.c. was noted to inhibit intestinal PGE<SUB>2</SUB> and the CPT11-related acute diarrheal symptoms, indicating that these diarrheal symptoms were mediated through the cholinergic nervous system accelerated functionally by CPT-11. On the other hand, daily treatment of CPT-11 at the same dose resulted in chronic diarrheal symptoms in all animals 3 days after CPT-11 treatment. Histopathological changes observed in the descending colon and ileum of the rats included degeneration and necrosis of villi and cryptal cells and a decrease in the number of the goblet cells. Significantly increased PGE<SUB>2</SUB> and impaired water absorption of the descending colon were also observed during the chronic diarrheal stage. It can be considered that the chronic diarrheal symptoms appear as a consequence of the gastrointestinal injury characterized by significant increase in PGE<SUB>2</SUB> accompanied by impaired water absorption.


  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 75(4), 399-405, 1997-12-01

    The Japanese Pharmacological Society

References:  25

Cited by:  2


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