Selenium-Containing Amino Acids Protect Dextran Sulfate Sodium-Induced Colitis via Ameliorating Oxidative Stress and Intestinal Inflammation

Abstract

Chengxin Shi,1,* Fengli Yue,2,* Feiyu Shi,1 Qian Qin,1 Lizhao Wang,1 Guanghui Wang,1 Lijun Mu,1 Dan Liu,1 Yaguang Li,1 Tianyu Yu,1 Junjun She1 1Department of General Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061, People’s Republic of China; 2College of Basic Medical Sciences, Jilin University, Changchun 130021, People’s Republic of China*These authors contributed equally to this workCorrespondence: Junjun SheDepartment of General Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, No. 277, Yanta West Road, Xi’an, Shaanxi 710061, People’s Republic of ChinaTel [phone]Email [email protected]: Inflammatory bowel disease (IBD) is characterized by chronic relapsing inflammation of the gastrointestinal tract. Oxidative stress plays a pivotal role in the pathogenesis of IBD. Selenium-containing amino acids reportedly have anti-oxidative and anti-inflammatory properties, but it remains unknown if selenium-containing amino acids can be used to treat IBD. This study aimed to investigate the effects of two selenium-containing amino acids – selenocysteine and selenocystine – on oxidative stress and chronic inflammation in a mouse model of dextran sulfate sodium (DSS)-induced IBD.Methodology: C57BL/6 mice were randomly assigned to the following six groups: control, DSS, DSS+selenocysteine, DSS+selenocystine, DSS+sodium selenite, and DSS+N-acetylcysteine (NAC). IBD was induced by 3% DSS. Pro-inflammatory cytokines [interleukin-1β (IL-1β), monocyte chemotactic protein 1 (MCP-1), IL-6, and tumor necrosis factor-α (TNF-α)] and markers for oxidative and anti-oxidative stress [malondialdehyde (MDA), reactive oxygen species (ROS), superoxide dismutase (SOD), and glutathione peroxidase (GPx)] were measured using immunohistochemical analysis.Results: Selenocysteine and selenocystine significantly attenuated IBD-related symptoms, including preventing weight loss, decreasing disease activity index (DAI) scores, and increasing colon length. Selenocysteine and selenocystine significantly ameliorated the DSS-induced oxidative stress, as demonstrated by a reduction in ROS and MDA activity and an increase in SOD and GPx activity. IL-1, MCP-1, IL-6, and TNF-α levels were significantly increased in the IBD mice, while treatment with the selenium-containing amino acids significantly reduced the levels of these pro-inflammatory cytokines. In vivo safety analysis showed minimal side effects of the selenium-containing amino acids.Conclusion: We found that selenocysteine and selenocystine ameliorated DSS-induced IBD via reducing oxidative stress and intestinal inflammation, indicating that selenium-containing amino acids could be a novel therapeutic option for patients with IBD.Keywords: Inflammatory bowel diseases, colitis, selenium-containing amino acids, selenocysteine, selenocystine, oxidative stress, inflammation

Keywords

• inflammatory bowel diseases
• colitis
• selenium-containing amino acids
• selenocysteine
• selenocystine
• oxidative stress
• inflammation