Quercetin as a potential blocker of liver fibrosis progression in rats with non-alcoholic steatosis hepatic (NASH): identification of therapeutic and prophylactic metabolic biomarkers

Author(s)

Raquel Arantes Megid

• Document type: Master's Dissertation
• Press: São José do Rio Preto. 2021-09-20.
• Institution: Universidade Estadual Paulista (Unesp). Instituto de Biociências Letras e Ciências Exatas. São José do Rio Preto
• Defense date: 2021-06-14
• Advisor: Fatima Pereira de Souza; Ícaro Putinhon Caruso

Abstract

Nonalcoholic fatty liver diseases (NAFLD) describe a spectrum of the most common and growing chronic liver diseases in the world, caused by accumulating fat in cells, a condition called steatosis. It is estimated that in one-fifth of the patients there is progression to the most severe stage of the disease, called nonalcoholic steatohepatitis (NASH), condition of hepatic steatosis with inflammation process, hepatocyte damage and potential development of fibrosis, cirrhosis, and hepatocellular carcinoma, situations of a potential need for liver transplantation. The quercetin molecule, a flavonoid present in the human diet, has a great pharmacological interest because it demonstrates the potential to reduce oxidative stress generated by the development of the disease. This work evaluates the therapeutic and prophylactic response of quercetin in the establishment of NASH. The Sprague-Dawley rats used as an experimental in vivo model were organized into five groups: Standard control (SC), that received a conventional diet nutritionally appropriate to the species; Hyperlipidic control + DEN (HD), hyperlipidic diet for EHNA induction and the hepatotoxic compound diethylnitrosamine (DEN); Hyperlipidic control (HC), hyperlipidic diet only; Prophylactic treatment (PT), hyperlipidic diet and simultaneous administration of quercetin since the beginning of the experiment; and Therapeutic treatment (TT), hyperlipidic diet and administration of quercetin three weeks after the experimental start. Were performed animal clinical performance evaluation, enzymatic kinetics analysis of ALT and AST transaminases, macroscopic and microscopic analysis of the liver and metabolomic identification by nuclear magnetic resonance (NMR). The animals in the SC Group demonstrated good clinical health conditions with normal standards in all variables analyzed. The HD Group was considered the group most attacked by the action of DEN together with the induction of NASH for presenting a set of common clinical characteristics in liver disorders such as jaundice, choluria and hypocholia, less body and liver weight gain, less food consumption, bigger serum ALT and AST levels and presence of fibrosis and liver cirrhosis. The animals in HC, PT and TT Groups presented the establishment of NASH, however, both treatments with quercetin were efficient and promising in order to prevent the establishment of fibrosis in the condition of NASH, protecting the organ against further degeneration and loss of vital functions, a fundamental aspect to guarantee the possibility of reversion of the pathology to the healthy clinical condition of the liver and recovery of its functions compromised by the accumulation of fat in the cells. (AU)

• FAPESP's process: 19/09253-5 - 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
• Grantee: Raquel Arantes Megid
• Support Opportunities: Scholarships in Brazil - Master