Center for Molecular Metabolism, Nanjing University of Science and Technology, 200 Xiaolingwei, Nanjing, 210094, Jiangsu, People's Republic of China.
Cancer Chemother Pharmacol. 2019 Jul;84(1):105-116. doi: 10.1007/s00280-019-03854-x. Epub 2019 May 8.
Methotrexate (MTX) is a widely used cancer chemotherapy agent. The efficacy of MTX is often limited by serious side effects, such as intestinal mucositis. The aim of this study was to evaluate the protective effect of water-soluble β-glucan salecan on MTX-induced intestinal toxicity in mice.
Intestinal mucositis was induced in C57BL/6 mice by intraperitoneal injection of MTX for two consecutive days. Mice were orally administrated with saline or salecan for 6 days before MTX injection and continued to the end of the study. Several histological and biochemical parameters were measured in the jejunum.
Orally administration of salecan improved the severity of intestinal mucositis in a dose-dependent manner, as evidenced by the well-maintained mucosal architecture and body weight in salecan-treated groups. Salecan treatment inhibited MTX-induced oxidative stress and effectively scavenged free radicals both in vitro and in vivo. Metabolomics analysis revealed that salecan treatment reversed the intestinal metabolic profiling changes in mice with MTX-induced mucositis. Salecan treatment modulated the innate immunity through the regulation of TLR and Dectin1 expression in the jejunum, thus protecting mice from MTX-induced intestinal damage.
Salecan has potential advantages in the treatment of MTX-induced intestinal mucositis, and its protective effect is mainly attributed to its antioxidant and immunomodulatory properties.
甲氨蝶呤（MTX）是一种广泛应用于癌症化疗的药物。然而，其疗效常受到严重副作用的限制，如肠道黏膜炎。本研究旨在评估水溶性 β-葡聚糖 salecan 对 MTX 诱导的小鼠肠道毒性的保护作用。
通过腹腔注射 MTX 连续两天诱导 C57BL/6 小鼠肠道黏膜炎。在 MTX 注射前 6 天，小鼠经口给予生理盐水或 salecan，并在研究结束时继续给药。在空肠中测量了几个组织学和生化参数。
Salecan 以剂量依赖的方式改善了肠道黏膜炎的严重程度，表现为黏膜结构完整和体重维持良好。Salecan 治疗抑制了 MTX 诱导的氧化应激，并在体外和体内有效地清除自由基。代谢组学分析表明，Salecan 治疗逆转了 MTX 诱导的黏膜炎小鼠的肠道代谢谱变化。Salecan 通过调节空肠中 TLR 和 Dectin1 的表达来调节先天免疫，从而保护小鼠免受 MTX 诱导的肠道损伤。
Salecan 在治疗 MTX 诱导的肠道黏膜炎方面具有潜在优势，其保护作用主要归因于其抗氧化和免疫调节特性。
