Methionine restriction on oxidative stress and immune response in dss-induced colitis mice

// Gang Liu 1 , Lei Yu 2 , Jun Fang 3 , Chien-An Andy Hu 1, 4 , Jie Yin 1 , Hengjia Ni 1 , Wenkai Ren 1 , Veeramuthu Duraipandiyan 5 , Shuai Chen 1 , Naif Abdullah Al-Dhabi 5 and Yulong Yin 1, 6, 7 1 Key Laboratory of Agro-Ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha 410125, China 2 China Animal Disease Control Center, Beijing 102618, China 3 College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha 410128, China 4 Department of Biochemistry and Molecular Biology, University of New Mexico School of Medicine, Albuquerque, New Mexico 87131, USA 5 Addiriyah Research Chair for Environmental Studies, Department of Botany and Microbiology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia 6 College of Animal Science, South China Agricultural University, Guangzhou 510642, China 7 Laboratory of Animal Nutrition and Human Health, School of Life Sciences, Hunan Normal University, Changsha 410081, China Correspondence to: Wenkai Ren, email: renwenkai19@126.com Yulong Yin, email: yinyulong@isa.ac.cn Keywords: inflammatory bowel disease, methionine restriction, diet, oxidative stress, NF-κB Received: December 28, 2016 Accepted: April 14, 2017 Published: May 11, 2017 ABSTRACT A strong correlation exists between inflammatory bowel disease (IBD) and oxidative stress involving alterations of several key signaling pathways. It is known that methionine promotes reactive oxygen species (ROS) production; we therefore hypothesize that a methionine restriction diet would reduce ROS production, inflammatory responses, and the course of IBD. We generated a murine colitis model by dextran sodium sulfate (DSS) treatment and tested the effects of the methionine restriction diet. Forty-eight mice were randomly divided into four groups of equal size, which included a control (CON) group, an MR (methionine restriction diet) group, a DSS treated group and an MR-DSS treated group. Mice in the first two groups had unrestricted access to water for one week. Mice in the two DSS-treated groups had unrestricted access to 5% DSS solution supplied in the drinking water for the same period. Mice in the CON and DSS groups were given a basal diet, whereas mice in the MR-DSS and MR groups were fed a 0.14% MR diet. We found that DSS reduced daily weight gain, suppressed antioxidant enzyme expression, increased histopathology scores and activated NF-κB and nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associated protein 1 (Nrf2/Keap1) signaling. We also showed that the MR diet upregulated catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities, decreased myeloperoxidase (MPO), TNF-α and IL-1β, and reversed activation of the NF-κB signaling pathway in MR-DSS mice. Taken together, our results imply that the MR diet may be considered as an adjuvant in IBD therapeutics.