β-ionone inhibits nonalcoholic fatty liver disease and its association with hepatocarcinogenesis in male Wistar rats

Mayara Lilian Paulino Miranda, Kelly Silva Furtado, Fábia de Oliveira Andrade, Renato Heidor, Raquel Santana da Cruz, Marina Sayuri Nogueira, Inar Alves de Castro, Eduardo Purgatto, Luis Fernando Barbisan, Fernando Salvador Moreno

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Among the primary neoplasias that affect the liver, hepatocellular carcinoma (HCC) is the most frequent and the third leading cause of death related to cancer. Several risk factors predispose individuals to HCC such as nonalcoholic fatty liver disease (NAFLD), whose incidence has significantly increased worldwide. β-ionone (βI) isoprenoid is a known chemopreventive of hepatocarcinogenesis. However, the effects of this compound on NAFLD isolated or in association with hepatocarcinogenesis have not yet been evaluated. A high-fat emulsion administered for 6 weeks resulted in NAFLD in male rats, and oral treatment with βI during this period significantly attenuated its development. Moreover, the presence of NAFLD potentiated hepatocarcinogenesis induced by the resistant hepatocyte (RH) model in these animals by increasing the number and percentage of the liver section area occupied by placental glutathione S-transferase (GST-P)-positive persistent preneoplastic lesions (pPNLs), that are thought to evolve into HCC. This indicates that this NAFLD/RH protocol is suitable for studies of the influence of NAFLD on the HCC development. Therefore, here we also investigated the chemopreventive effect of βI under these two associated conditions. In this context, βI reduced the number and percentage of the liver section area occupied by pPNLs, as well as cell proliferation and the number of oval cells, which are considered potential targets for the development of HCC. Thus, βI presents not only a promising inhibitory effect on NAFLD isolated but also chemopreventive activity when it is associated with hepatocarcinogenesis.

Original languageEnglish (US)
Pages (from-to)377-384
Number of pages8
JournalChemico-Biological Interactions
Volume308
DOIs
StatePublished - Aug 1 2019
Externally publishedYes

Bibliographical note

Funding Information:
The authors thank the National Council for Scientific and Technological Development ( Conselho Nacional de Desenvolvimento Científico e Tecnológico- CNPq ), the Coordination for the Improvement of Higher Education Personnel (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior CAPES) and Foundation for Research Support of the State of São Paulo ( Fundação de Apoio à Pesquisa do Estado de São Paulo – FAPESP , process number 2013/07914-8 ) for the financial support.

Publisher Copyright:
© 2019

Keywords

  • Chemoprevention
  • Hepatocarcinogenesis
  • Isoprenoids and beta-ionone
  • NAFLD

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