Jaboticaba, Malay apple and black plum: effects of polyphenol-rich fruits on fibrosis-associated hepatocarcinogenesis

• Grant number: 17/17516-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: March 01, 2018
• End date: February 28, 2019
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal Investigator: Luís Fernando Barbisan
• Grantee: Isadora Penedo de Souza
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Globally, the hepatocellular carcinoma (HCC) is the 6th most common cancer and the 4th cause of cancer-related deaths in women. On the other hand, epidemiological studies indicate that vegetable consumption leads to a reduction in HCC risk: for every 100 g/day the risk is reduced by 8% to 17%. In the last years, anthocyanin-rich fruits of Myrtaceae family, jaboticaba (Myrciaria cauliflora), malay apple (Syzygium malaccense) and black plum (Syzygium cumini), raised scientific interest for their notable antioxidant capacity and, thus, potential for the prevention and/or treatment of chronic diseases. Therefore, the study will evaluate whether the ingestion of dehydrated jaboticaba, malay apple or black plum peels attenuate fibrosis-associated hepatocarcinogenesis in mice. Then, female C3H/HeJ mice will receive a single intraperitoneal (i.p.) diethylnitrosamine injection (10 mg/Kg body weight [b.wt.], in 0.9% saline) 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., 10% corn oil solution). Besides, from 7th to 17th week, mice will received basal diets containing (2%) of dehydrated jaboticaba, malay apple or black plum peels. Mice will be euthanized at the end of 17th week of experiment. Liver samples will be collected for histopathological analysis (incidence, number, size and area of hepatocellular preneoplastic lesions in HE-stained sections), fibrosis and collagen morphometric analysis (Sirius Red) and immunohistochemistry for Ki-67 (i.e. cell proliferation), cleaved caspase-3 (i.e. apoptosis) and ±-smooth muscle actin (i.e. hepatic stellate cell marker). Liver will be also sampled for antioxidant profiling analysis (levels of reduced and total glutathione, activity of glutathione peroxidase and S-transferase, catalase and superoxide dismutase) and lipid hydroperoxide level determination. Serum samples will be collected for alanine and aspartate aminotransferases determinations. Data will be analyzed by ANOVA or Kruskal-Wallis and post hoc Tukey or Dunn's, respectively (p<0.05). The analysis of dehydrated peels by high performance liquid chromatography revealed high levels of antioxidant anthocyanins in all fruit peels. (AU)

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; DE SOUZA, ISADORA PENEDO; DE SOUZA, LUCAS VILHEGAS; PRATA, GABRIEL BACIL; DE CAMPOS FRAGA-SILVA, THAIS FERNANDA; SARTORI, ALEXANDRINA; BORGUINI, RENATA GALHARDO; DE ARAUJO SANTIAGO, MANUELA CRISTINA PESSANHA; HENRIQUE FERNANDES, ANA ANGELICA; COGLIATI, BRUNO; et al. Beneficial effects of anthocyanin-rich peels of Myrtaceae fruits on chemically-induced liver fibrosis and carcinogenesis in mice. Food Research International, v. 139, JAN 2021. (16/14420-0, 17/17516-0)