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Cadmium Induces Acute Liver Injury by Inhibiting Nrf2 and the Role of NF-κB, NLRP3, and MAPKs Signaling Pathway

Author

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  • Chang Liu

    (Key Laboratory of Quality & Safety Control for Pork, Ministry of Agriculture and Rural, College of Animal Science, Anhui Science and Technology University, Fengyang 233100, China
    Equally contributed to this paper.)

  • Yaohui Zhu

    (Key Laboratory of Quality & Safety Control for Pork, Ministry of Agriculture and Rural, College of Animal Science, Anhui Science and Technology University, Fengyang 233100, China
    Equally contributed to this paper.)

  • Zhenxiang Lu

    (Key Laboratory of Quality & Safety Control for Pork, Ministry of Agriculture and Rural, College of Animal Science, Anhui Science and Technology University, Fengyang 233100, China)

  • Weina Guo

    (Key Laboratory of Quality & Safety Control for Pork, Ministry of Agriculture and Rural, College of Animal Science, Anhui Science and Technology University, Fengyang 233100, China)

  • Bayaer Tumen

    (Shanxi Animal Disease Control Center, Taiyuan 030027, China)

  • Yalan He

    (Key Laboratory of Quality & Safety Control for Pork, Ministry of Agriculture and Rural, College of Animal Science, Anhui Science and Technology University, Fengyang 233100, China)

  • Chao Chen

    (Key Laboratory of Quality & Safety Control for Pork, Ministry of Agriculture and Rural, College of Animal Science, Anhui Science and Technology University, Fengyang 233100, China)

  • Shanshan Hu

    (Key Laboratory of Quality & Safety Control for Pork, Ministry of Agriculture and Rural, College of Animal Science, Anhui Science and Technology University, Fengyang 233100, China)

  • Kangzhi Xu

    (Key Laboratory of Quality & Safety Control for Pork, Ministry of Agriculture and Rural, College of Animal Science, Anhui Science and Technology University, Fengyang 233100, China)

  • Yan Wang

    (Key Laboratory of Quality & Safety Control for Pork, Ministry of Agriculture and Rural, College of Animal Science, Anhui Science and Technology University, Fengyang 233100, China)

  • Lei Li

    (Key Laboratory of Quality & Safety Control for Pork, Ministry of Agriculture and Rural, College of Animal Science, Anhui Science and Technology University, Fengyang 233100, China)

  • Shenghe Li

    (Key Laboratory of Quality & Safety Control for Pork, Ministry of Agriculture and Rural, College of Animal Science, Anhui Science and Technology University, Fengyang 233100, China)

Abstract

Acute Cadmium (Cd) exposure usually induces hepatotoxicity. It is well known that oxidative stress and inflammation causes Cd-induced liver injury. However, the effect of nuclear factor erythroid 2-related factor 2 (Nrf2) in Cd-induced liver injury is not completely understood. In this study, we observed Cd-induced liver damage and the potential contribution of Nrf2, nuclear factor-κB (NF-κB), Nod-like receptor 3 (NLRP3), and mitogen-activated protein kinases (MAPKs) signaling pathways. Changes in serum transaminases and proinflammatory cytokines expression showed that Cd could induce acute hepatotoxicity. Moreover, Nrf2 and its downstream heme oxygenase 1 (HO-1) were inhibited by Cd exposure, and Kelch-like ECH-associated protein 1 (Keap1), the inhibitory protein of Nrf2, was increased. Furthermore, NF-κB, NLRP3, and MAPKs signaling pathways were all activated by Cd intoxication. In conclusion, the inhibition of Nrf2, HO-1, and the activation of NF-κB, NLRP3, and MAPKs all contribute to Cd-induced liver injury.

Suggested Citation

  • Chang Liu & Yaohui Zhu & Zhenxiang Lu & Weina Guo & Bayaer Tumen & Yalan He & Chao Chen & Shanshan Hu & Kangzhi Xu & Yan Wang & Lei Li & Shenghe Li, 2019. "Cadmium Induces Acute Liver Injury by Inhibiting Nrf2 and the Role of NF-κB, NLRP3, and MAPKs Signaling Pathway," IJERPH, MDPI, vol. 17(1), pages 1-10, December.
    • Handle: RePEc:gam:jijerp:v:17:y:2019:i:1:p:138-:d:301383
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    References listed on IDEAS

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    1. Rongbin Zhou & Amir S. Yazdi & Philippe Menu & Jürg Tschopp, 2011. "A role for mitochondria in NLRP3 inflammasome activation," Nature, Nature, vol. 469(7329), pages 221-225, January.
    2. Rongbin Zhou & Amir S. Yazdi & Philippe Menu & Jürg Tschopp, 2011. "Erratum: A role for mitochondria in NLRP3 inflammasome activation," Nature, Nature, vol. 475(7354), pages 122-122, July.
    3. Milena Andjelkovic & Aleksandra Buha Djordjevic & Evica Antonijevic & Biljana Antonijevic & Momcilo Stanic & Jelena Kotur-Stevuljevic & Vesna Spasojevic-Kalimanovska & Milos Jovanovic & Novica Boricic, 2019. "Toxic Effect of Acute Cadmium and Lead Exposure in Rat Blood, Liver, and Kidney," IJERPH, MDPI, vol. 16(2), pages 1-21, January.
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    1. Iwona Markiewicz-Górka & Małgorzata Chowaniec & Helena Martynowicz & Anna Wojakowska & Aleksandra Jaremków & Grzegorz Mazur & Piotr Wiland & Krystyna Pawlas & Rafał Poręba & Paweł Gać, 2022. "Cadmium Body Burden and Inflammatory Arthritis: A Pilot Study in Patients from Lower Silesia, Poland," IJERPH, MDPI, vol. 19(5), pages 1-19, March.

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    More about this item

    Keywords

    Cadmium; acute liver injury; Nrf2; NLRP3; NF-κB; MAPKs;
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