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Evaluation of the effect of NS1 protein and quercetin as potential blockers in the progression of hepatic fibrosis in rats with NASH: identification of therapeutic and prophylactic metabolic biomarkers

Grant number: 19/09253-5
Support type:Scholarships in Brazil - Master
Effective date (Start): January 01, 2020
Effective date (End): February 28, 2021
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Fátima Pereira de Souza
Grantee:Raquel Arantes Megid
Home Institution: Instituto de Biociências, Letras e Ciências Exatas (IBILCE). Universidade Estadual Paulista (UNESP). Campus de São José do Rio Preto. São José do Rio Preto , SP, Brazil

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a growing cause of chronic liver disease all over the world. This disease affects individuals who develop steatohepatitis (NASH), which can progress to fibrosis in 20 to 40% of cases, with 10% progressing to cirrhosis and 1-5% hepatocellular carcinoma (HCC). In the presence of NASH, hyperinsulinemia, adipose inflammation and hypoadiponectinemia deregulate the turnover of one or more hepatic lipid reservoirs, accumulating lipid molecules that affect hepatocytes and lead to inflammation, elevating the expression of IL-6 and TNF-±, important proinflammatory cytokines. The hRSV NS1 protein performs an important function in block of the immune response, once decreases cytokine expression, including TNF-± / ², IFN-± / ², IFN-³ and nuclear factor kappa ² (NF-k²), interleukins as IL-1± and IL-6 and inhibits apoptosis of infected host cells. The reduction of TNF-± and IL-6 expression has also been described by the use of quercetin, a molecule that has reduce oxidative stress potential. The aim of this study is to evaluate the therapeutic and prophylactic response of NS1 and quercetin in rats with NASH and hepatic fibrosis induced by a choline deficient hyperlipidemic diet (CHD). The prophylactic and therapeutic effect of the use of these molecules will be evaluated by immunohistochemical, histopathological techniques, quantification of pro-inflammatory and pro-fibrotic cytokines by Elisa, and metabolites generated by NMR. As a result, we hope to find biomarkers: metabolic, of diagnostic involved in the progression of NASH to liver fibrosis; and therapeutic, that respond to the modulation and decrease of the inflammatory process in the liver by the use of NS1 and quercetin or their combination. (AU)