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
| Autor: | Divya Gupta, Love Sharma, Sheikh Tasduq Abdullah |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Time Factors Inflammation Thioacetamide Diet High-Fat Liver Cirrhosis Experimental Toxicology Collagen Type I High cholesterol Cholesterol Dietary Palmitic acid 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Non-alcoholic Fatty Liver Disease Transforming Growth Factor beta Fibrosis Cell Line Tumor Internal medicine Hepatic Stellate Cells medicine Animals Humans Cytochrome P-450 CYP2E1 General Medicine CYP2E1 medicine.disease Actins Collagen Type I alpha 1 Chain Mice Inbred C57BL 030104 developmental biology Endocrinology Liver chemistry Hepatocytes Collagen medicine.symptom Steatohepatitis 030217 neurology & neurosurgery Transforming growth factor |
| Zdroj: | Toxicology Letters. 304:21-29 |
| ISSN: | 0378-4274 |
| DOI: | 10.1016/j.toxlet.2019.01.001 |
| Popis: | 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-s, 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. |
| Databáze: | OpenAIRE |
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