Although an antitumor drug 5-fluorouracil (5-FU) frequently causes intestinal mucositis accompanied by severe diarrhea, the useful prevention and treatment have not been established. Glutamate is known to play an important role in energy metabolism in gastrointestinal tracts. The aim of this study was to investigate the alleviative effect of 5-FU-induced mucositis in mice. Intestinal mucositis was induced in male C57BL/6 mice by repeated administration of 5-FU for 6 days. Glutamate was administered orally starting from 5 days before the onset of 5-FU treatment. Disease severity was assessed by body weight and stool consistency, and the intestinal mucositis was examined histologically. The effect of glutamate on 5-FU-induced cell injury was also examined in rat intestinal epithelial cell line IEC6.
Repeated administration of 5-FU produced severe intestinal mucositis, histologically characterized by the shortening of villi and destruction of crypts, accompanied by body weight loss and diarrhea. Daily administration of glutamate significantly reduced the severity of histological intestinal injury despite little preventive effect on diarrhea and body weight loss. The pretreatment with glutamate significantly increased epithelial electrical resistance in IEC6 cells. These results suggest that glutamate prevents 5-FU-induced intestinal mucositis via enhancement of intestinal barrier functions. Thus, glutamate administration may be useful for prevention and treatment of intestinal mucositis during cancer chemotherapy.