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Chlorogenic acid and indole-3-carbinol: effects of bioactive compounds of Brassica vegetables in nonalcoholic steatohepatitis in vivo

Grant number: 20/01944-6
Support type:Scholarships in Brazil - Master
Effective date (Start): September 01, 2020
Effective date (End): February 28, 2022
Field of knowledge:Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
Principal Investigator:Luís Fernando Barbisan
Grantee:Gabriel Bacil Prata
Home Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Nowadays, it is estimated that non-alcoholic fatty liver disease (NAFLD) affects about 25% of the world population. Non-alcoholic steatohepatitis (NASH), the most severe level of NAFLD, affects about 5% of the world population. Histologically, NAFLD ranges from hepatic steatosis, characterized by the accumulation of lipids in the form of macrovesicles or microvesicles, to NASH, which simultaneously presents the occurrence of inflammatory processes and the onset of fibrosis to the lipid deposit. NAFLD has no effective treatment, other than changing eating habits and performing physical exercises. The consumption of the Western diet, rich in saturated fats and sugars (fructose and glucose), figures as the main responsible for the development of NAFLD. On the other hand, adherence to the Mediterranean diet, rich in polyphenolic compounds, carotenoids and unsaturated fats, is associated with a reduction in the severity of NAFLD. Brassica vegetables (cauliflower, broccoli, kale, among others) are traditionally consumed in the diet and are rich in bioactive compounds with antioxidant and anti-inflammatory properties.Among them, chlorogenic acid (ACG) and indole-3-carbinol (I3C) are highlighted, which associate these properties with the ability to modulate lipid biosynthesis in the liver. Thus, the effects of the administration of ACG and/or I3C on the nutritional/chemical induction NASH will be evaluated.For this purpose, male C57BL/6J mice (10 animals/group) will receive a basal diet and filtered water or a diet rich in lipids (20% lard) and sucrose (20%) and a solution rich in sugars (23.1 g/L and 18.9 g/L of d-fructose and d-glucose, respectively), in addition to three weekly intraperitoneal (i.p.) doses of 10% carbon tetrachloride (CCl4) solution, diluted in corn oil, with initial concentration of 0.25¼L / g body weight (p.c.) and end of 1.50¼L/g p.c. or vehicle, for 8 weeks. Concomitantly, the animals will receive ACG (125mg/kg p.c.) alone, I3C (5mg/kg p.c.) alone, the combination of the two substances or only the deionized water vehicle (intragastric route, 5 times/week). The doses were defined according to the calculation of the equivalent dose in humans (600 and 22.5 mg/day of ACG and I3C, respectively). The animals' glycemic curve will be drawn and then they will be euthanized after the 8th week. Hepatic samples will be obtained for histological analysis (severity of NAFLD, fibrosis and immunohistochemistry for Ki67, CD68 and ±-smooth muscle actin), molecular (evaluation of IL-6, IL-1², IL-10, TNF-±, TGF-± , TGF-² and NF-ºB) and biochemistry (profile of fatty acids, triglycerides, cholesterol and alaninaminotransferase). Epididymal adipose tissue will be used for histology (morphometry, mast cell infiltration and immunohistochemistry for CD68). (AU)