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Article

Low simvastatin concentrations reduce oleic acid-induced steatosis in HepG2 cells: An in vitro model of non-alcoholic fatty liver disease

  • Authors:
    • Mohammad J. Alkhatatbeh
    • Lisa F. Lincz
    • Rick F. Thorne
  • View Affiliations / Copyright

    Affiliations: Clinical Pharmacy Department, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid 22110, Jordan, Hunter Haematology Research Group, Calvary Mater Newcastle Hospital, Waratah, NSW 2298, Australia, School of Environmental and Life Sciences, University of Newcastle, Ourimbah, NSW 2258, Australia
  • Pages: 1487-1492
    |
    Published online on: February 10, 2016
       https://doi.org/10.3892/etm.2016.3069
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Abstract

Non-alcoholic fatty liver disease (NAFLD) is an inflammatory condition caused by hepatic lipid accumulation that is associated with insulin resistance, diabetes and metabolic syndrome. Although statins should be used with caution in liver diseases, they are increasingly investigated as a possible treatment for NAFLD. The present study recreated an in vitro model of NAFLD using HepG2 cells exposed to oleic acid (OA), which was used to quantify OA-induced lipid accumulation in HepG2 cells treated with various concentrations of simvastatin. In addition, the effect of simvastatin on HepG2 cell morphology and microparticle generation as a marker of cell apoptosis was assessed. OA‑induced lipid accumulation was quantified by Oil Red O staining and extraction for optical density determination. Stained lipid droplets were visualized using phase contrast microscopy. Furthermore, HepG2 cell‑derived microparticles were counted by flow cytometry subsequent to staining for Annexin V. HepG2 cells treated with 0‑1 mM OA showed dose‑dependent lipid accumulation. Treatment of HepG2 cells with increasing concentrations of simvastatin followed by treatment with 1 mM OA showed that low simvastatin concentrations (4‑10 µM) were able to reduce lipid accumulation by ~40%, whereas high simvastatin concentrations (20 and 30 µM) induced apoptotic changes in cell morphology and increased the production of Annexin V+ microparticles. This suggests that low simvastatin doses may have a role in preventing NAFLD. However, further investigations are required to confirm this action in vivo and to determine the underlying mechanism by which simvastatin reduces hepatic steatosis.
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Copy and paste a formatted citation
Spandidos Publications style
Alkhatatbeh MJ, Lincz LF and Thorne RF: Low simvastatin concentrations reduce oleic acid-induced steatosis in HepG2 cells: An in vitro model of non-alcoholic fatty liver disease. Exp Ther Med 11: 1487-1492, 2016.
APA
Alkhatatbeh, M.J., Lincz, L.F., & Thorne, R.F. (2016). Low simvastatin concentrations reduce oleic acid-induced steatosis in HepG2 cells: An in vitro model of non-alcoholic fatty liver disease. Experimental and Therapeutic Medicine, 11, 1487-1492. https://doi.org/10.3892/etm.2016.3069
MLA
Alkhatatbeh, M. J., Lincz, L. F., Thorne, R. F."Low simvastatin concentrations reduce oleic acid-induced steatosis in HepG2 cells: An in vitro model of non-alcoholic fatty liver disease". Experimental and Therapeutic Medicine 11.4 (2016): 1487-1492.
Chicago
Alkhatatbeh, M. J., Lincz, L. F., Thorne, R. F."Low simvastatin concentrations reduce oleic acid-induced steatosis in HepG2 cells: An in vitro model of non-alcoholic fatty liver disease". Experimental and Therapeutic Medicine 11, no. 4 (2016): 1487-1492. https://doi.org/10.3892/etm.2016.3069
Copy and paste a formatted citation
x
Spandidos Publications style
Alkhatatbeh MJ, Lincz LF and Thorne RF: Low simvastatin concentrations reduce oleic acid-induced steatosis in HepG2 cells: An in vitro model of non-alcoholic fatty liver disease. Exp Ther Med 11: 1487-1492, 2016.
APA
Alkhatatbeh, M.J., Lincz, L.F., & Thorne, R.F. (2016). Low simvastatin concentrations reduce oleic acid-induced steatosis in HepG2 cells: An in vitro model of non-alcoholic fatty liver disease. Experimental and Therapeutic Medicine, 11, 1487-1492. https://doi.org/10.3892/etm.2016.3069
MLA
Alkhatatbeh, M. J., Lincz, L. F., Thorne, R. F."Low simvastatin concentrations reduce oleic acid-induced steatosis in HepG2 cells: An in vitro model of non-alcoholic fatty liver disease". Experimental and Therapeutic Medicine 11.4 (2016): 1487-1492.
Chicago
Alkhatatbeh, M. J., Lincz, L. F., Thorne, R. F."Low simvastatin concentrations reduce oleic acid-induced steatosis in HepG2 cells: An in vitro model of non-alcoholic fatty liver disease". Experimental and Therapeutic Medicine 11, no. 4 (2016): 1487-1492. https://doi.org/10.3892/etm.2016.3069
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