Metabolic effects of p-coumaric acid in the perfused rat liver.
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 (IC50 values of 92.5 and 75.6 microM, 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 (IC50 = 160.1 microM); 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 beta-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.
Department of Biochemistry, University of Maringá, 87020900 Maringá, Brazil.
Leonardo C N
LC
Lima
Gisele D
GD
Buss
Emy L
EL
Ishii-Iwamoto
Clairce
C
Salgueiro-Pagadigorria
Jurandir Fernando
JF
Comar
Adelar
A
Bracht
Jorgete
J
Constantin
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D003373:Coumaric Acids / Q000494:pharmacology*; D005943:Gluconeogenesis / Q000187:drug effects*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism*; D010477:Perfusion; D011422:Propionates; D051381:Rats; D017208:Rats, Wistar
D000975:Antioxidants; D003373:Coumaric Acids; D011422:Propionates; C495469:p-coumaric acid