PREVENTIVE EFFECTS OF HANGE-SHASHIN-TO ON IRINOTECAN HYDROCHLORIDE-CAUSED DIARRHEA AND ITS RELEVANCE TO THE COLONIC PROSTAGLANDIN E-2 AND WATER-ABSORPTION IN THE RAT

The possible preventive effect of Kampo medicine Hange-shashin-to (TJ- 14) on chronic diarrheal symptoms induced by the administration of the anticancer agent irinotecan hydrochloride (CPT-11) was investigated i n the rat. Repeated oral administrations of TJ-14 at 125 and 500 mg/kg significantly prevented the reduction in body weight and the onset of chronic diarrheal symptoms due to CPT-11 in a dose-dependent manner, even though it failed to show a definite effect on acute diarrheal sym ptoms. In addition, treatment with TJ-14 accelerated the healing of th e intestinal tract injured by repeated dosing of CPT-11 and inhibited significantly the increase of colonic prostaglandin E-2 (PGE(2)) which is closely related to the onset of diarrhea. TJ-14 also improved colo nic water absorption impaired by repeated dosing of CPT-11 in rats. Th ese results demonstrate that TJ-14 is an effective medicine for the pr evention and/or treatment of CPT-ll-induced chronic diarrheal symptoms .