Metabolic effects of p-coumaric acid in the perfused rat liver

✍ Scribed by Leonardo C.N. Lima; Gisele D. Buss; Emy L. Ishii-Iwamoto; Clairce Salgueiro-Pagadigorria; Jurandir Fernando Comar; Adelar Bracht; Jorgete Constantin

• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: English
• Weight: 165 KB
• Volume: 20
• Category: Article
• ISSN: 1095-6670
• DOI: 10.1002/jbt.20114

✦ Synopsis

Abstract

The p‐coumaric acid, a phenolic acid, occurs in several plant species and, consequently, in many foods and beverages of vegetable origin. Its antioxidant activity is well documented, but there is also a single report about an inhibitory action on the monocarboxylate carrier, which operates in the plasma and mitochondrial membranes. The latter observation suggests that p‐coumaric acid could be able to inhibit gluconeogenesis and related parameters. The present investigation was planned to test this hypothesis in the isolated and hemoglobin‐free perfused rat liver. Transformation of lactate and alanine into glucose (gluconeogenesis) in the liver was inhibited by p‐coumaric acid (IC~50~ values of 92.5 and 75.6 μM, respectively). Transformation of fructose into glucose was inhibited to a considerably lower degree (maximally 28%). The oxygen uptake increase accompanying gluconeogenesis from lactate was also inhibited. Pyruvate carboxylation in isolated intact mitochondria was inhibited (IC~50~ = 160.1 μM); no such effect was observed in freeze–thawing disrupted mitochondria. Glucose 6‐phosphatase and fructose 1,6‐bisphosphatase were not inhibited. In isolated intact mitochondria, p‐coumaric acid inhibited respiration dependent on pyruvate oxidation but was ineffective on respiration driven by succinate and β‐hydroxybutyrate. It can be concluded that inhibition of pyruvate transport into the mitochondria is the most prominent primary effect of p‐coumaric acid and also the main cause for gluconeogenesis inhibition. The existence of additional actions of p‐coumaric acid, such as enzyme inhibitions and interference with regulatory mechanisms, cannot be excluded. © 2006 Wiley Periodicals, Inc. J Biochem Mol Toxicol 20:18–26, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20114