title: Pyrrolidine Dithiocarbamate Inhibits NF-KappaB Activation and Upregulates the Expression of Gpx1, Gpx4, Occludin, and ZO-1 in DSS-Induced Colitis.
abstract: Inflammatory bowel disease (IBD) correlates with oxidative stress, inflammation, and alteration in several signal pathways, including nuclear transcription factor-kappaB (NF-κB). Pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-κB, has been widely demonstrated to exhibit an antioxidant and anti-inflammatory function. This study aimed to test the hypothesis that NF-κB inhibitor PDTC confers a beneficial role in a colitis model induced by dextran sodium sulfate (DSS) in mouse. The results showed that DSS decreased daily weight gain, induced colonic inflammation, suppressed the expression of antioxidant enzymes and tight junctions, and activated NF-κB and nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associated protein 1 (Nrf2/Keap1) signaling pathways. PDTC significantly upregulated (P < 0.05) Gpx1, Gpx4, occludin, and ZO-1 expressions in the DSS-induced colitis model. Meanwhile, PDTC reversed (P < 0.05) the activation of NF-κB signal pathway caused by DSS treatment. In conclusion, PDTC could serve as an adjuvant therapy for the patient with IBD.
authors.affiliation: Scientific Observing and Experimental Station of Animal Nutrition and Feed Science in South-Central, Ministry of Agriculture, Hunan Provincial Engineering Research Center of Healthy Livestock, Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, Hunan, 410125, China.|University of Chinese Academy of Sciences, Beijing, 100039, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yin
authors.affiliation: Scientific Observing and Experimental Station of Animal Nutrition and Feed Science in South-Central, Ministry of Agriculture, Hunan Provincial Engineering Research Center of Healthy Livestock, Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, Hunan, 410125, China.|University of Chinese Academy of Sciences, Beijing, 100039, China.
authors.forename: Miaomiao
authors.initials: M
authors.lastname: Wu
authors.affiliation: Scientific Observing and Experimental Station of Animal Nutrition and Feed Science in South-Central, Ministry of Agriculture, Hunan Provincial Engineering Research Center of Healthy Livestock, Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, Hunan, 410125, China.|University of Chinese Academy of Sciences, Beijing, 100039, China.
authors.forename: Jielin
authors.initials: J
authors.lastname: Duan
authors.affiliation: Scientific Observing and Experimental Station of Animal Nutrition and Feed Science in South-Central, Ministry of Agriculture, Hunan Provincial Engineering Research Center of Healthy Livestock, Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, Hunan, 410125, China. gangle.liu@gmail.com.
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.affiliation: Scientific Observing and Experimental Station of Animal Nutrition and Feed Science in South-Central, Ministry of Agriculture, Hunan Provincial Engineering Research Center of Healthy Livestock, Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, Hunan, 410125, China.|University of Chinese Academy of Sciences, Beijing, 100039, China.
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Cui
authors.affiliation: College of Animal Science, Hunan Agricultural University, Changsha, Hunan, 410128, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Scientific Observing and Experimental Station of Animal Nutrition and Feed Science in South-Central, Ministry of Agriculture, Hunan Provincial Engineering Research Center of Healthy Livestock, Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, Hunan, 410125, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Chen
authors.affiliation: Scientific Observing and Experimental Station of Animal Nutrition and Feed Science in South-Central, Ministry of Agriculture, Hunan Provincial Engineering Research Center of Healthy Livestock, Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, Hunan, 410125, China.
authors.forename: Wenkai
authors.initials: W
authors.lastname: Ren
authors.affiliation: College of Animal Science, Hunan Agricultural University, Changsha, Hunan, 410128, China.
authors.forename: Jinping
authors.initials: J
authors.lastname: Deng
authors.affiliation: Department of Laboratory Animal Science, University of South China, Hengyang, 421001, China.
authors.forename: Xiangwen
authors.initials: X
authors.lastname: Tan
authors.affiliation: Department of Botany and Microbiology, Addiriyah Chair for Environmental Studies, College of Science, King Saud University, P.O. Box 2455, Riyadh, 11451, Saudi Arabia.
authors.forename: Naif Abdullah
authors.initials: NA
authors.lastname: Al-Dhabi
authors.affiliation: Department of Botany and Microbiology, Addiriyah Chair for Environmental Studies, College of Science, King Saud University, P.O. Box 2455, Riyadh, 11451, Saudi Arabia.
authors.forename: Veeramuthu
authors.initials: V
authors.lastname: Duraipandiyan
authors.affiliation: Scientific Observing and Experimental Station of Animal Nutrition and Feed Science in South-Central, Ministry of Agriculture, Hunan Provincial Engineering Research Center of Healthy Livestock, Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, Hunan, 410125, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Liao
authors.affiliation: Scientific Observing and Experimental Station of Animal Nutrition and Feed Science in South-Central, Ministry of Agriculture, Hunan Provincial Engineering Research Center of Healthy Livestock, Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, Hunan, 410125, China. tjli@isa.ac.cn.
authors.forename: Tiejun
authors.initials: T
authors.lastname: Li
authors.affiliation: Scientific Observing and Experimental Station of Animal Nutrition and Feed Science in South-Central, Ministry of Agriculture, Hunan Provincial Engineering Research Center of Healthy Livestock, Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, Hunan, 410125, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Yulong
mesh_terms: D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D016207:Cytokines / Q000235:genetics; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D005979:Glutathione Peroxidase / Q000235:genetics; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000378:metabolism*; D062793:Occludin / Q000235:genetics; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D011759:Pyrrolidines / Q000008:administration & dosage*; D015398:Signal Transduction; D013859:Thiocarbamates / Q000008:administration & dosage*; D062826:Zonula Occludens-1 Protein / Q000235:genetics; D000094765:Glutathione Peroxidase GPX1
chemical_list: D016207:Cytokines; D016328:NF-kappa B; D062793:Occludin; D011759:Pyrrolidines; D013859:Thiocarbamates; C569043:Tjp1 protein, mouse; D062826:Zonula Occludens-1 Protein; C020972:pyrrolidine dithiocarbamic acid; D016264:Dextran Sulfate; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D005979:Glutathione Peroxidase; C000611332:glutathione peroxidase 4, mouse; D000094765:Glutathione Peroxidase GPX1; C000722068:Gpx1 protein, mouse
keywords: Antioxidant gene; IBD; NF-κB; PDTC; Tight junction