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Camel whey protein alleviates heat stress-induced liver injury by activating the Nrf2/HO-1 signaling pathway and inhibiting HMGB1 release

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Cell Stress and Chaperones Aims and scope

Abstract

This study aimed to investigate the mechanism by which camel whey protein (CWP) inhibits the release of high-mobility group box 1 (HMGB1) in heat stress (HS)-stimulated rat liver. Administration of CWP by gavage prior to HS inhibited the cytoplasmic translocation of HMGB1 and consequently reduced the inflammatory response in the rat liver, and downregulated the levels of the NLR pyrin domain containing 3 (NLRP3) inflammasome, interleukin (IL)-1β, and tumor necrosis factor (TNF)-α. The use of N-acetyl-L-cysteine (NAC), an inhibitor of reactive oxygen species (ROS) production, indicated that this downregulation effect may be attributed to the antioxidant activity of CWP. We observed that CWP enhanced nuclear factor erythroid 2-related factor (Nrf)2 and heme-oxygenase (HO)-1 expression, which inhibited ROS production, nicotinamide adenine dinucleotide phosphate oxidase (NOX) activity, and malondialdehyde (MDA) levels, and increased superoxide dismutase 1 (SOD1) activity and reduced glutathione (GSH) content in the HS-treated liver, ultimately increasing the total antioxidant capacity (TAC) in the liver. Administration of Nrf2 or HO-1 inhibitors before HS abolished the protective effects of CWP against oxidative damage in the liver of HS-treated rats, accompanied by increased levels of HMGB1 in the cytoplasm and IL-1β and TNF-α in the serum. In conclusion, our study demonstrated that CWP enhanced the TAC of the rat liver after HS by activating Nrf2/HO-1 signaling, which in turn reduced HMGB1 release from hepatocytes and the subsequent inflammatory response and damage. Furthermore, the combination of CWP and NAC abolished the adverse effects of HS in the rat liver. Therefore, dietary CWP could be an effective adjuvant treatment for HS-induced liver damage.

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Acknowledgements

The authors would like to acknowledge the support through funds.

Funding

This research was funded by National Natural Science Foundation of China (32060815), and Natural Science Foundation of Inner Mongolia (2020MS03011).

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Authors and Affiliations

  1. Key Laboratory of Clinical Diagnosis and Treatment Technology in Animal Disease/Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot, 010018, China

    Donghua Du, Wenting Lv, Xiaoxia Jing, Chunwei Yu, Jiya Wuen & Surong Hasi

  2. Department of Veterinary Medicine, College of Animal Science and Technology, Hebei North University, Zhangjiakou, 075131, Hebei, China

    Donghua Du & Wenting Lv

  3. Inner Mongolia Institute of Camel Research, Alashan, 750300, Inner Mongolia, China

    Surong Hasi

Authors
  1. Donghua Du
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  2. Wenting Lv
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  3. Xiaoxia Jing
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  4. Chunwei Yu
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  5. Jiya Wuen
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  6. Surong Hasi
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Contributions

Study concept and design: Donghua Du, Surong Hasi. Acquisition of data: Donghua Du, Wenting Lv, Xiaoxia Jing. Analysis and interpretation of data: Chunwei Yu, Jiya Wuen. Drafting of the manuscript: Donghua Du, Wenting Lv, Xiaoxia Jing. Critical revision of the manuscript for important intellectual content: Surong Hasi. Administrative, technical, or material support, study supervision: Surong Hasi.

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Correspondence to Surong Hasi.

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Du, D., Lv, W., Jing, X. et al. Camel whey protein alleviates heat stress-induced liver injury by activating the Nrf2/HO-1 signaling pathway and inhibiting HMGB1 release. Cell Stress and Chaperones 27, 449–460 (2022). https://doi.org/10.1007/s12192-022-01277-x

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  • DOI: https://doi.org/10.1007/s12192-022-01277-x

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