Histone deacetylase inhibitors: Opening a new field of research in the development of alternative methods?

In the present study, the ability of the hydroxamate histone deacetylase (HDAC) inhibitor 4-Me2N-BAVAH (5-(4-dimethylaminobenzoyl)-aminovaleric acid hydroxamate) to prevent dedifferentiation in cultures of primary hepatocytes is investigated. To this end, rat hepatocytes were isolated in the presence of 50μM 4-Me2N-BAVAH and exposure was subsequently continued for 7 days in monolayer culture (0.05% v/v ethanol-exposed cultures served as vehicle controls). It was found that in the continuous presence of 4-Me2NBAVAH, albumin secretion into the culture medium was 2.9and 5.3-fold higher when compared to the control results after 4 and 7 days of cultivation, respectively. CYP1A1 was re-expressed after 4 days culture, but declined again thereafter, whilst CYP2B1 protein levels were maintained throughout the culture time in 4-Me2N-BAVAH-treated cells. In addition, pro-caspase-3 cleavage was significantly reduced after 7 days, pointing to decreased apoptosis and thus improved survival in the 4-Me2N-BAVAH-exposed hepatocytes. These findings provide additional evidence that HDAC inhibitors could play a major role in the preservation of the differentiated hepatic phenotype in vitro.