Journal
LIFE SCIENCES
Volume 260, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2020.118404
Keywords
Animal model; NAFLD; Hypoxia; HFCD; NASH; Inflammation; Fibrosis
Funding
- Translational Health Science and Technology Institute (THSTI) Core Fund
- Translational Research Project (TRP) Fund
- Department of Biotechnology (DBT)
- Indian Council of Medical Research [3/1/2(19)/OBS/2019-NCD-II]
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Aim: NAFLD is a chronic and progressive disease for which there are no FDA-approved drugs available in the market. Drug discovery is a time-consuming procedure and requires screening of hundreds of small molecules to find new chemical entities (NECs) for a particular disease. Current preclinical NAFLD animal models take a longer time, which enhances the duration and expenses of the screening procedure. Hence to shorten the duration, we have proposed a preclinical animal model for rapid induction of non-alcoholic steatohepatitis (NASH), an advanced stage of NAFLD in rats. Methodology: The animals were divided into three groups; control, high fat choline deficient (HFCD) and high fat choline deficient diet with sodium nitrite (40 mg/kg b.w. i.p. per day) (HFCD + NaNO2) respectively. Four weeks later physical and serum biochemical parameters were assessed, intraperitoneal glucose tolerance test was performed, and histopathology and gene expression were analysed. Key findings: Hypoxic stress aggravates the lipid accumulation, ballooning, lobular inflammation and fibrosis in hepatic tissue in presence of HFCD diet. Significance: This novel rodent model could be a useful NAFLD model to screen small molecules rapidly for treatment of NASH.
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