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Sleep deprivation aggravated lipopolysaccharide/d-galactosamine-induced acute liver injury by suppressing melatonin production

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Abstract

Objective

Sleep loss is common in patients with liver injury, but the effects of sleep deprivation (SD) on liver injury remain unclear. In the present study, the potential effects of SD on acute liver injury and the underlying mechanisms have been investigated.

Methods

The sleep of male BALB/c mice has been deprived by using a modified multiple platform water bath for 3 days and acute liver injury was induced by intraperitoneal injection of lipopolysaccharide (LPS) and d-galactosamine (D-Gal). The degree of liver injury was detected by aminotransferase determination, histopathology and survival rate analysis. Inflammatory response and melatonin (MT) were measured by enzyme-linked immunosorbent assay (ELISA). In addition, hepatocyte apoptosis was determined by caspase activity measurement and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay.

Results

We observed that SD increased plasma aminotransferases, TUNEL-positive hepatocytes, histological abnormalities and mortality rates in mice with LPS/D-Gal treatment. SD also promoted LPS/D-Gal-induced production of TNF-α and upregulated hepatic caspase-8, caspase-9, and caspase-3 activities in LPS/D-Gal-exposed mice. In addition, SD significantly decreased MT contents in plasma of mice with acute liver injury, but supplementation with MT reversed these SD-promoted changes.

Conclusion

Our data suggested that SD exacerbated LPS/D-Gal-induced liver injury via decreasing melatonin production.

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Acknowledgements

This study was supported by the Natural Science Foundation of Chongqing, China (No. cstc2018jcyjAX0682).

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Author notes

  1. Lu Liu and Li Zhang contributed equally to this work.

Authors and Affiliations

  1. Department of Rehabilitation Medicine and Physical Therapy, The Affiliated Rehabilitation Hospital of Chongqing Medical University, 50 Xiejiawan Cultural Seventh Village, Jiulongpo District, Chongqing, 400050, China

    Lu Liu

  2. Department of Pathophysiology, Chongqing Medical University, 1 Yixueyuan Road, Chongqing, 400016, China

    Li Zhang, Longjiang Li, Yi Shen & Jiayi Huang

  3. Department of Neurology, The Affiliated Rehabilitation Hospital of Chongqing Medical University, 50 Xiejiawan Cultural Seventh Village, Jiulongpo District, Chongqing, 400050, China

    Mengting Chen

  4. Department of Neurology, University-Town Hospital of Chongqing Medical University, 55 Middle Road, University City, Shapingba District, Chongqing, 401331, China

    Zhe Wang & Ling Tang

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  1. Lu Liu
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Correspondence to Ling Tang.

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Liu, L., Zhang, L., Li, L. et al. Sleep deprivation aggravated lipopolysaccharide/d-galactosamine-induced acute liver injury by suppressing melatonin production. Inflamm. Res. 69, 1133–1142 (2020). https://doi.org/10.1007/s00011-020-01393-3

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  • DOI: https://doi.org/10.1007/s00011-020-01393-3

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