グルタミン酸は5-フルオロウラシル誘起腸炎を抑制する

• Published in: 日本薬理学会年会要旨集 p. 1-B-SS01-2
• Main Authors: 上南, 静佳, 天ヶ瀬, 紀久子, 加藤, 伸一
• Format: Journal Article
• Language: Japanese
• Published: 公益社団法人 日本薬理学会 2023
• Subjects: apoptosis; epithelium; glutamic acid; intestine
• ISSN: 2435-4953
• DOI: 10.1254/jpssuppl.97.0_1-B-SS01-2

While 5-Fluorouracil (5-FU) is the widely used chemotherapeutic agent, it often causes mucoenteritis with severe diarrhea, nausea, vomiting, and body weight loss. These conditions are related with impaired quality of life of patients with cancer. Glutamate (Glu) is a nonessential amino acid and the most important energy source in the small intestine. In this study, we aimed to evaluate the role of Glu on the 5-FU-induced mucoenteritis. Mucoenteritis was induced in male C57B/6N mice by repeated administration of 5-FU (50 mg/kg, i.p.). Glu was administered as a pretreatment for 7 days before the initial treatment of 5-FU. Disease severity was assessed by histological and physiological analysis. Moreover, cell proliferation, apoptosis, and intestinal permeability were assessed using immunohistochemistry. The effect of Glu on 5-FU-induced cell injury was also examined in IEC-6, rat intestinal epithelial cell line. The pretreatment with Glu significantly suppressed the histological changes, impairment of cell proliferation, and apoptosis by 5-FU. While the expression of excitatory amino acid transporters (EAAT) was decreased on the ileum tissue damaged by 5-FU, Glu treatment maintained a high expression level of EAAT. These results suggest that Glu prevents 5-FU-induced mucoenteritis via enhancement of Glu transporters. Thus, Glu administration may have protective effects on 5-FU-induced mucoenteritis.