Thioacetamide potentiates high cholesterol and high fat diet induced steato-hepatitic changes in livers of C57BL/6J mice: A novel eight weeks model of fibrosing NASH

Toxicol Lett. 2019 Apr;304:21-29. doi: 10.1016/j.toxlet.2019.01.001. Epub 2019 Jan 6.


There is an inadequacy of relevant animal models to study non-alcoholic steatohepatitis (NASH) and fibrosis. Here, we co-administered thioacetamide (TH) along with fast food diet (FFD) to C57BL/6 J mice for eight weeks. The treatments were: a) standard chow, SC b) FFD c) FFD + TH [75 mg/kg], FTH d) SC + TH [150 mg/kg], STH for 8 weeks. In in-vitro model, Hep3B cells were exposed to palmitic acid (PA) and TH viz. PA (0.25 mM) + TH (25 mM), PA (0.5 mM) alone and TH (50 mM) alone for 12 h, later supernatant media was transferred to LX-2 cells, for another 12 h. Molecular and cellular events related to inflammation, fibrosis, collagen deposition were studied. The FTH mice featured hepatic inflammation, severe diffuse fibrosis, and collagen deposition, which were less severe in FF & STH groups. In FTH group the protein expressions of α-SMA, TGF-ß, Col1 A1, CYP2E1, were up-regulated as compared to the FF group. The in-vivo findings were complemented in the LX-2 and Hep3B cells. The protein expressions of inflammatory and cellular injury markers were significantly higher in PA + TH exposed LX-2 cells. This novel model manifested hepatic inflammation and fibrosis in just eight weeks, which may be exploited for rapid screening of novel anti-NAFLD and liver anti-fibrotic agents.

Keywords: Fast food diet; Fibrosis; NAFLD; NASH; Thioacetamide.

MeSH terms

  • Actins / metabolism
  • Animals
  • Cell Line, Tumor
  • Cholesterol, Dietary*
  • Collagen / metabolism
  • Collagen Type I / metabolism
  • Collagen Type I, alpha 1 Chain
  • Cytochrome P-450 CYP2E1 / metabolism
  • Diet, High-Fat*
  • Hepatic Stellate Cells / metabolism
  • Hepatic Stellate Cells / pathology
  • Hepatocytes / metabolism
  • Hepatocytes / pathology
  • Humans
  • Liver / metabolism
  • Liver / pathology*
  • Liver Cirrhosis, Experimental / chemically induced*
  • Liver Cirrhosis, Experimental / metabolism
  • Liver Cirrhosis, Experimental / pathology
  • Male
  • Mice, Inbred C57BL
  • Non-alcoholic Fatty Liver Disease / chemically induced*
  • Non-alcoholic Fatty Liver Disease / metabolism
  • Non-alcoholic Fatty Liver Disease / pathology
  • Thioacetamide*
  • Time Factors
  • Transforming Growth Factor beta / metabolism


  • Actins
  • Cholesterol, Dietary
  • Collagen Type I
  • Collagen Type I, alpha 1 Chain
  • Transforming Growth Factor beta
  • alpha-smooth muscle actin, mouse
  • Thioacetamide
  • Collagen
  • Cytochrome P-450 CYP2E1