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Bioactive coffee compounds and their effects on liver fibrosis

Grant number: 17/16596-0
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): January 01, 2018
Effective date (End): December 31, 2019
Field of knowledge:Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
Principal researcher:Luís Fernando Barbisan
Grantee:Gabriel Bacil Prata
Home Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil


Epidemiological data indicates that liver fibrosis/cirrhosis leads to one billion deaths annually. The fibrosis pathogenesis is considered a complex and dynamic process, involving extracellular matrix, hepatic stellate cells (HSCs), macrophages and metalloproteinases (MMP) interactions. Under the fibrosis/cirrhosis context, there is increased susceptibility for the emerging of hepatocellular carcinoma, the second leading cause of cancer-related deaths. On the other hand, coffee beverage consumption reduces by 40% the risk for liver fibrosis, while decaffeinated consumption does not. Among many compounds present in coffee beverages, caffeine, trigonelline and chlorogenic acid (CGA) are some of the most abundant. Thus, the present study will evaluate whether the consumption of caffeine alone or associated to trigonelline and/or chlorogenic acid attenuates liver fibrosis. Male C3H/HeJ mice will receive a single diethylnitrosamine injection (intraperitoneal [i.p.], 10 mg/Kg body weight [b.wt.]) at 14th postnatal day. From 8th to 16th week, mice will receive three weekly doses of carbon tetrachloride (initial dose of 0.25 ¼L/g b.wt. and there will be 0.25 mg weekly increments to the utmost dose of 1.50 ¼L/g b.wt.). Besides, from 7th to 17th week, mice will receive (1x/day, 5x/week) caffeine (50 mg/Kg b.wt./day), caffeine and trigonelline (50 and 25 mg/Kg b.wt./day, respectively); caffeine and CGA (50 and 25 mg/Kg b.wt./day); caffeine, trigonelline and CGA (50, 25 e 25 mg/Kg b.wt./day) or just distilled water vehicle. Mice will be euthanized at the end of 17th week of experiment. Liver samples will be collected for fibrosis and collagen morphometric analysis (Picro Sirius Red), immunohistochemistry (±-smooth muscle actin, i.e. HSCs marker; F4/80, i.e. macrophage marker), western blot (TGF-B1 and p65 [NF-kB]) and gelatin zymography (MMP-2 e 9). Data will be analyzed by ANOVA or Kruskal-Wallis and post hoc Tukey or Dunn's, respectively (p<0.05). (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
ROMUALDO, GUILHERME RIBEIRO; PRATA, GABRIEL BACIL; DA SILVA, TEREZA CRISTINA; EVANGELISTA, ADRIANE FEIJO; REIS, RUI MANUEL; VINKEN, MATHIEU; MORENO, FERNANDO SALVADOR; COGLIATI, BRUNO; BARBISAN, LUIS FERNANDO. The combination of coffee compounds attenuates early fibrosis-associated hepatocarcinogenesis in mice: involvement of miRNA profile modulation. JOURNAL OF NUTRITIONAL BIOCHEMISTRY, v. 85, NOV 2020. Web of Science Citations: 0.

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