粘膜炎
昂丹司琼
医学
药理学
细胞凋亡
内科学
化疗
恶心
生物
生物化学
作者
Masashi Yasuda,Shinichi Kato,Naoaki Yamanaka,Maho Iimori,Kenjiro Matsumoto,Daichi Utsumi,Yumeno Kitahara,Kikuko Amagase,Syunji Horie,Koji Takeuchi
摘要
Background and Purpose Chemotherapeutic agents, including 5‐fluorouracil (5‐ FU ), frequently cause intestinal mucositis resulting in severe diarrhoea and morphological mucosal damage. 5‐ HT 3 receptor antagonists are clinically effective in the treatment of nausea and emesis during cancer chemotherapy. Therefore we here have examined the effects of 5‐ HT 3 receptor antagonists on 5‐ FU ‐induced intestinal mucositis in mice. Experimental Approach Intestinal mucositis was induced in male C57BL /6 mice by daily administration of 5‐ FU (50 mg·kg −1 ) for 5 days. Effects of 5‐ HT 3 receptor antagonists, ramosetron (0.01–0.1 mg·kg −1 ) and ondansetron (5 mg·kg −1 ), on the accompanying histology, cytokine production and apoptosis were assessed. Key Results Continuous administration of 5‐ FU to mice caused severe intestinal mucositis, which was histologically characterized by the shortening of villi and destruction of intestinal crypts, accompanied by body weight loss and diarrhoea. Daily ramosetron administration dose‐dependently reduced the severity of intestinal mucositis, body weight loss and diarrhoea. Similar beneficial effects were observed with ondansetron. The number of apoptotic, caspase‐3‐ and caspase‐8‐activated cells increased 24 h after the first 5‐ FU administration, and these responses were reduced by ramosetron. The up‐regulation of TNF ‐α, IL ‐1β and IL ‐6 following 5‐ FU treatment was also attenuated by ramosetron. Conclusions and Implications 5‐ HT 3 receptor antagonists ameliorated 5‐ FU ‐induced intestinal mucositis in mice, and this action could result from suppression of apoptotic responses in the intestinal crypt cells via inhibition of cytokine expression. Thus, 5‐ HT 3 receptor antagonists may be useful for preventing not only nausea and emesis but also intestinal mucositis during 5‐ FU chemotherapy.
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