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Pyrrolidine Dithiocarbamate Inhibits NF-KappaB Activation and Upregulates the Expression of Gpx1, Gpx4, Occludin, and ZO-1 in DSS-Induced Colitis

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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.

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Abbreviations

IBD:

Inflammatory bowel disease

NF-κB:

Nuclear transcription factor-kappa B

PDTC:

Pyrrolidine dithiocarbamate

DSS:

Dextran sodium sulfate

Nrf2:

Nuclear factor erythroid 2-related factor 2

Keap1:

Kelch-like ECH-associated protein 1

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Acknowledgments

This study was supported by the National Natural Science Foundation of China (No. 31272463); Hunan Provincial Natural Science Foundation (No. 12JJ2014, 13JJ2034); China Scholarship Council; and King Saud University, Deanship Scientific Research, College of Science, Research Center.

Compliance with Ethical Standards

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Ethics Approval

The experiment was carried out in accordance with the Chinese guidelines for animal welfare and experimental protocol, and was approved by the Animal Care and Use Committee of the Institute of Subtropical Agriculture, Chinese Academy of Sciences.

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Authors and Affiliations

  1. 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

    Jie Yin, Miaomiao Wu, Jielin Duan, Gang Liu, Zhijie Cui, Shuai Chen, Wenkai Ren, Peng Liao, Tiejun Li & Yin Yulong

  2. University of Chinese Academy of Sciences, Beijing, 100039, China

    Jie Yin, Miaomiao Wu, Jielin Duan & Zhijie Cui

  3. College of Animal Science, Hunan Agricultural University, Changsha, Hunan, 410128, China

    Jie Zheng & Jinping Deng

  4. Department of Laboratory Animal Science, University of South China, Hengyang, 421001, China

    Xiangwen Tan

  5. Department of Botany and Microbiology, Addiriyah Chair for Environmental Studies, College of Science, King Saud University, P.O. Box 2455, Riyadh, 11451, Saudi Arabia

    Naif Abdullah Al-Dhabi & Veeramuthu Duraipandiyan

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  1. Jie Yin
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  2. Miaomiao Wu
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  4. Gang Liu
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  15. Yin Yulong
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Corresponding authors

Correspondence to Gang Liu or Tiejun Li.

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Jie Yin and Miaomiao Wu contributed equally to this work.

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Yin, J., Wu, M., Duan, J. et al. Pyrrolidine Dithiocarbamate Inhibits NF-KappaB Activation and Upregulates the Expression of Gpx1, Gpx4, Occludin, and ZO-1 in DSS-Induced Colitis. Appl Biochem Biotechnol 177, 1716–1728 (2015). https://doi.org/10.1007/s12010-015-1848-z

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