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Diallyl disulfide attenuates non‑alcoholic steatohepatitis by suppressing key regulators of lipid metabolism, lipid peroxidation and inflammation in mice

  • Authors:
    • Ning Zhang
    • Yuli Wang
    • Junli Zhang
    • Beibei Liu
    • Guixin Li
    • Shengliang Xin
    • Keshu Xu

  • View Affiliations

  • Published online on: May 31, 2019     https://doi.org/10.3892/mmr.2019.10316
  • Pages: 1363-1372
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
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Abstract

Non‑alcoholic steatohepatitis (NASH) is a common clinicopathological condition. Currently, the pathogenesis of NASH remains unknown, and no optimal therapy option currently exists. It has previously been demonstrated that diallyl disulfide (DADS) was capable of attenuating liver dysfunction, as DADS supplementation had a positive impact on liver regeneration, proliferation and oxidative damage. Thus, DADS could serve as a potential therapeutic agent that can protect against the effects of NASH. The present study aimed to evaluate the effect of DADS on NASH and to understand the associated underlying molecular mechanisms. A methionine‑ and choline‑deficient diet (MCD) and high‑fat diet (HFD) are the two common animal models that induce NASH. C57BL/6J mice were fed an MCD for 4 weeks, or an HFD for 20 weeks, in the present study. The mice were treated with or without DADS (20, 50 and 100 mg/kg) for 4 or 20 weeks. For the histopathological examination, hematoxylin and eosin staining, oil red O staining and immunohistochemical analyses were performed using the liver sections. Biochemical assays and ELISA were performed to measure the serum biochemical indicators of hepatic function and inflammatory indicators, respectively. Reverse transcription‑quantitative PCR, immunofluorescence and western blotting were used to detect expression levels of the genes involved in the molecular mechanisms underlying DADS protection. MCD or HFD induced the histological features of NASH in mice, including significant vacuolated hepatocytes, marked inflammatory cell infiltration and severe micro‑ and macro‑vesicular steatosis. Serum alanine transferase and aspartate aminotransferase levels, as well as the contents of liver triglyceride and total cholesterol, were significantly increased in these two models. DADS attenuated these histological and biochemical changes. DADS ameliorated hepatic steatosis by regulating sterol regulatory element‑binding transcription factor 1, apolipoprotein A1, cyclic AMP‑responsive element‑binding protein H and fibroblast growth factor 21. Furthermore, DADS was revealed to prevent lipotoxicity via peroxisome proliferator‑activated receptor α elevation and stearoyl‑coenzyme A desaturase 1 inhibition in HFD‑fed mice. In addition, DADS markedly inhibited lipid peroxidation by modulating malondialdehyde and superoxide dismutase, and it also decreased tumor necrosis factor‑α production, interleukin‑6 production and macrophage influx, as well as suppressing nuclear factor‑κB activation, indicating suppression of MCD‑induced hepatic inflammation. Taken together, the results have shown that DADS exerts beneficial effects on MCD‑ or HFD‑induced NASH by suppressing key regulators of lipid metabolism, lipid peroxidation and inflammation.
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August-2019
Volume 20 Issue 2

Print ISSN: 1791-2997
Online ISSN:1791-3004

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  • Journal Metrics
  • Impact Factor: 3.4
  • Ranked Medicine Research and Experimental
    (total number of cites)
  • CiteScore: 7.6
  • CiteScore Rank: Q1: #82/347 Biochemistry, Genetics and Molecular Biology
  • Source Normalized Impact per Paper (SNIP): 0.647
  • SCImago Journal Rank (SJR): 0.781
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Spandidos Publications style
Zhang N, Wang Y, Zhang J, Liu B, Li G, Xin S and Xu K: Diallyl disulfide attenuates non‑alcoholic steatohepatitis by suppressing key regulators of lipid metabolism, lipid peroxidation and inflammation in mice. Mol Med Rep 20: 1363-1372, 2019.
APA
Zhang, N., Wang, Y., Zhang, J., Liu, B., Li, G., Xin, S., & Xu, K. (2019). Diallyl disulfide attenuates non‑alcoholic steatohepatitis by suppressing key regulators of lipid metabolism, lipid peroxidation and inflammation in mice. Molecular Medicine Reports, 20, 1363-1372. https://doi.org/10.3892/mmr.2019.10316
MLA
Zhang, N., Wang, Y., Zhang, J., Liu, B., Li, G., Xin, S., Xu, K."Diallyl disulfide attenuates non‑alcoholic steatohepatitis by suppressing key regulators of lipid metabolism, lipid peroxidation and inflammation in mice". Molecular Medicine Reports 20.2 (2019): 1363-1372.
Chicago
Zhang, N., Wang, Y., Zhang, J., Liu, B., Li, G., Xin, S., Xu, K."Diallyl disulfide attenuates non‑alcoholic steatohepatitis by suppressing key regulators of lipid metabolism, lipid peroxidation and inflammation in mice". Molecular Medicine Reports 20, no. 2 (2019): 1363-1372. https://doi.org/10.3892/mmr.2019.10316