Phenylbutyrate (PBA) is an aromatic
short-chain fatty acid which is a chemical derivative of
butyric acid naturally produced by colonic bacteria fermentation. At the intestinal level
butyrate exerts a multitude of activities including amelioration of mucosal
inflammation, regulation of transepithelial fluid transport, improvement in oxidative status and
colon cancer prevention. Moreover, increasing number of studies report the beneficial role of
butyric acid in prevention or inhibition of other types of
malignancies, leading to
cancer cell growth arrest and apoptosis. Similarly, phenylbutyrate displays potentially favorable effects on many pathologies including
cancer, genetic
metabolic syndromes, neuropathies, diabetes,
hemoglobinopathies, and
urea cycle disorders. The mechanisms by which PBA exerts these effects are different. Some of them are connected with the regulation of gene expression, playing the role of a
histone deacetylase inhibitor, while others contribute to the ability of rescuing conformational abnormalities of
proteins, serving as chemical chaperone, and some are dedicated to its metabolic characteristic enabling excretion of toxic
ammonia, thus acting as
ammonia scavenger. Phenylbutyrate may exert variable effects depending on the cell type, thus the term "
butyrate paradox" has been proposed. These data indicate a broad spectrum of beneficial effects evoked by PBA with a high potential in
therapy. In this review, we focus on cellular and systemic effects of PBA treatment with special attention to the three main branches of its molecular activity:
ammonia scavenging, chaperoning and
histone deacetylase inhibiting, and describe its particular role in various human diseases.