Chemopreventive effects of the dietary histone deacetylase inhibitor tributyrin alone or in combination with vitamin A during the promotion phase of rat hepatocarcinogenesis | Health & Environmental Research Online (HERO)

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Citation
Tags

HERO ID

2280992

Reference Type

Journal Article

Title

Chemopreventive effects of the dietary histone deacetylase inhibitor tributyrin alone or in combination with vitamin A during the promotion phase of rat hepatocarcinogenesis

Author(s)

de Conti, A; Kuroiwa-Trzmielina, J; Horst, MA; Bassoli, BK; Chagas, CEA; Purgatto, E; Cavalher, FP; Camargo, AA; Jordao, AA, Jr; Vannucchi, H; Scolastici, C; Ong, TP; Moreno, FS

Year

2012

Is Peer Reviewed?

Journal

Journal of Nutritional Biochemistry
ISSN: 0955-2863
EISSN: 1873-4847

Volume

Issue

Page Numbers

860-866

Language

English

PMID

21940155

DOI

10.1016/j.jnutbio.2011.04.010

Web of Science Id

WOS:000306880100002

Abstract

The chemopreventive effects of tributyrin (TB) and vitamin A (VA), alone or in combination, were investigated during the promotion phase of rat hepatocarcinogenesis. Compared to diethylnitrosamine control rats, TB and TB+VA-treated rats, but not VA-treated rats, presented a lower incidence and mean number of hepatocyte nodules and a smaller size of persistent preneoplastic lesions (pPNLs). In addition, TB and TB+VA-treated rats exhibited a higher apoptotic body index in pPNL and remodeling PNL, whereas VA-treated rats presented only a higher apoptotic body index in remodeling PNL. None of the treatments inhibited cell proliferation in PNL. TB and TB+VA-treated rats, but not VA-treated rats, exhibited higher levels of H3K9 acetylation and p21 protein expression. TB and VA-treated rats exhibited increased hepatic concentrations of butyric acid and retinoids, respectively. Compared to normal rats, diethylnitrosamine control animals exhibited lower retinyl palmitate hepatic concentrations. All groups had similar expression levels and exhibited similar unmethylated CRBP-I promoter region in microdissected pPNL, indicating that epigenetic silencing of this gene was not involved in alteration of retinol metabolism in early hepatocarcinogenesis. Data support the effectiveness of TB as a dietary histone deacetylase inhibitor during the promotion phase of hepatocarcinogenesis, which should be considered for chemoprevention combination strategies.

Keywords

Chemoprevention; Hepatocarcinogenesis; Tributyrin; Vitamin A; Epigenetic