Yan Gao1, Qi Sun1, Xiao Yang1, Weiling Lu1, Yang Zhao1, Wenhao Ge1, Yunxia Yang1, Xi Xu1, Jianfa Zhang2. 1. Center for Molecular Metabolism, Nanjing University of Science and Technology, 200 Xiaolingwei, Nanjing, 210094, Jiangsu, People's Republic of China. 2. Center for Molecular Metabolism, Nanjing University of Science and Technology, 200 Xiaolingwei, Nanjing, 210094, Jiangsu, People's Republic of China. jfzhang@mail.njust.edu.cn.
Abstract
PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
PURPOSE: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. METHODS: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. RESULTS: 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. CONCLUSIONS: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.