THE ACTIONS OF CARBENOXOLONE ON GLYCOGEN CATABOLISM AND OXYGEN CONSUMPTION IN LIVERS OF FED RATS

Abstract

Carbenoxolone is a derivative of glycyrrhetinic acid, the active principle of licorice (Glycyrrhiza glabra), a medicinal root. The pharmacological properties attributed to carbenoxolone are related to its inhibitory actions on the 11β-hydroxysteroid dehydrogenase and gap junction channels. Recent studies have shown that carbenoxolone also induces swelling and membrane potential collapse in mitochondria. These effects were related to hydrogen peroxide generation and mitochondrial permeability transition (MPT) induction, indicating possible toxicological actions of carbenoxolone at the mitochondrial level, which could trigger the apoptotic pathway. The data of these previous reports are pointing, thus, in the direction of a possible action of carbenoxolone on the bioenergetic functions of mitochondria, which could in turn cause toxic metabolic changes in the liver. For this reason, the present work was planned to investigate if carbenoxolone affects glycogenolysis and glycolysis in the rat liver. Male Wistar rats, weighing 180 to 220 g, fed with a standard laboratory diet were utilized. The isolated liver was perfused in the non-recirculating system. The perfusion fluid was Krebs/Henseleit-bicarbonate buffer (pH 7.4), saturated with a mixture of O2 and CO2 (95:5) by means of a membrane oxygenator and simultaneously heated to 37oC. For measuring glycogen catabolism (glycogenolysis and glycolysis) livers from ad libitum fed rats were utilized. In livers from fed rats carbenoxolone increased oxygen uptake, glycolysis and glycogenolysis, which is an expected combination of phenomena for decreased mitochondrial ATP formation.