癌症继续对全球健康构成重大挑战，其中胃肠道 (GI) 癌症是最常见和最致命的癌症形式之一。这些癌症通常导致高死亡率并需要使用强效细胞毒性化疗药物。例如，5-氟尿嘧啶 (5-FU) 构成了包括结直肠癌在内的各种胃肠道癌症化疗方案的支柱。虽然这些化疗药物能有效杀死癌细胞，但它们经常引起脱靶效应，例如化疗引起的粘膜炎 (CIM)，其特征是疼痛、恶心和腹泻等衰弱症状，需要医疗干预。在这项研究中，我们阐明了褪黑激素和米索前列醇减少 5-FU 诱发的小肠粘膜炎的潜力。对大鼠空肠的形态和细胞变化以及结肠粪便水含量进行量化，作为 CIM 的标记。此外，还在体外研究了褪黑激素对 5-FU 处理的小鼠肠道类器官的影响。结果表明，褪黑激素可防止大鼠空肠粘膜绒毛萎缩，并维持小鼠肠道类器官中的细胞活力。相比之下，米索前列醇单独使用或与褪黑激素联合使用并没有显着影响5-FU引起的CIM。这些体内和体外实验提供了有希望的见解，即褪黑激素可以用作预防和/或辅助联合疗法来预防和减少 CIM，从而有可能增强癌症治疗结果并改善患者的生活质量。版权所有：© 2024 彼得斯等人。这是一篇根据知识共享署名许可条款分发的开放获取文章，允许在任何媒体上不受限制地使用、分发和复制，前提是注明原始作者和来源。

Cancer continues to pose a significant global health challenge, with gastrointestinal (GI) cancers among the most prevalent and deadly forms. These cancers often lead to high mortality rates and demand the use of potent cytotoxic chemotherapeutics. For example, 5-fluorouracil (5-FU) forms the backbone of chemotherapy regimens for various GI cancers, including colorectal cancer. While these chemotherapeutics efficiently kill cancer cells, they frequently cause off-target effects such as chemotherapy-induced mucositis (CIM), characterized by debilitating symptoms like pain, nausea, and diarrhoea, necessitating medical intervention. In this study, we elucidated the potential of melatonin and misoprostol to reduce 5-FU-induced small intestinal mucositis. Morphological and cellular changes in the jejunum, along with colonic faecal water content were quantified in rats as markers for CIM. Additionally, the effects of melatonin were investigated in vitro on 5-FU treated murine intestinal organoids. The results showed that melatonin prevented villus atrophy in the rat jejunal mucosa and upheld cell viability in murine intestinal organoids. In contrast, misoprostol alone or in combination with melatonin did not significantly affect CIM caused by 5-FU. These in vivo and in vitro experiments provided promising insights that melatonin may be used as a preventive and/or adjuvant combination therapy to prevent and reduce CIM, holding the potential to enhance cancer treatment outcomes and improve patient quality-of-life.Copyright: © 2024 Peters et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.