Structured lipids obtained from intersterification of tributyrin and flax seed oil and their chemopreventive potential during early promotion phase of experimental hepatocarcinogenesis in rats

Author(s)

Juliana Festa Ortega

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ)
• Defense date: 2016-01-08

Examining board members

Fernando Salvador Moreno; Bruno Cogliati; Maria Lucia Zaidan Dagli; Maria Aparecida Azevedo Koike Folgueira; Juliana Neves Rodrigues Ract

• Advisor: Fernando Salvador Moreno

Abstract

Combination of chemopreventive agents with different mechanisms of action has been considered a promising strategy to cancer prevention. Among several bioactive food compounds, tributyrin, a butyric acid prodrug obtained from dairy products and dietetic fiber fermentation, and flax seed oil, a rich source of alpha linolenic acid have shown chemopreventive potential. Here, we evaluated the chemopreventive activity of structured lipids obtained by enzymatic interesterification of tributyrin and flax seed oil during the early promotion phase of experimental hepatocarcinogenesis. Male Wistar rats subjected to the resistant hepatocyte model were treated daily, i.g, with maltodextrin, flax seed oil, tributyrin, non-sterified blend, or structured lipids. Treatment structured lipids showed similar chemopreventive activity compared to tributyrin, even when structured lipids yielded lower concentrations of butyric in the liver. Tributyrin and structured lipids did not inhibit cell proliferation in preneoplastic lesions, but both of them induced apoptosis in remodeling preneoplastic lesions. In addition, histone acetylation and p21 restored expression tributyrin molecular mechanisms were related to modulation of p53 nuclear shuttling mechanisms. In the present study, it was observed a substantial increase in p53 nuclear/cytoplasmic ratio and importin-alpha in preneoplastic livers of tributyrin treated rats, but not in those treated with structured lipids. In contrast, treatment structured lipids downregulated expression of major oncogenes Bcl2, Ccnd2, Pdgfa, and Vegfa; and upregulated expression of critical tumor suppressor genes, Cdh13, Socs3 and Fhit. Hence, although structured lipids and tributyrin show similar chemopreventive potential, the results suggest that the new compound does not exhibit HDACi activity, and that its inhibitory effects may be attributed to the modulation of oncogenes and tumor suppressor genes expression. (AU)

• FAPESP's process: 12/00498-6 - Strutured lipids obteined from intersterification of tributyrin and flax seed oil and their chemopreventive potential during promotion phase of experimental hepatocarcinogenesis
• Grantee: Juliana Festa Ortega
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)