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

Chem Biol Interact. 2019 Aug 1:308:377-384. doi: 10.1016/j.cbi.2019.05.046. Epub 2019 May 28.

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.

Keywords: Chemoprevention; Hepatocarcinogenesis; Isoprenoids and beta-ionone; NAFLD.

MeSH terms

  • Administration, Oral
  • Animals
  • Apoptosis / drug effects
  • Carcinoma, Hepatocellular / chemically induced
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / prevention & control*
  • Cell Proliferation / drug effects
  • Glutathione Transferase / metabolism
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Liver Neoplasms / pathology
  • Liver Neoplasms / prevention & control*
  • Male
  • Non-alcoholic Fatty Liver Disease / chemically induced
  • Non-alcoholic Fatty Liver Disease / pathology
  • Non-alcoholic Fatty Liver Disease / prevention & control*
  • Norisoprenoids / pharmacology
  • Norisoprenoids / therapeutic use*
  • Oxidative Stress / drug effects
  • Rats
  • Rats, Wistar
  • Triglycerides / analysis

Substances

  • Norisoprenoids
  • Triglycerides
  • beta-ionone
  • Glutathione Transferase