THE ACTIONS OF CARBENOXOLONE ON FRUCTOSE CATABOLISM IN LIVERS OF FASTED 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 gluconeogenesis in the rat liver. Livers from 24 h fasted Male Wistar rats weighing 200 to 280 g were used in the experiments. The isolated liver was perfused in the non-recirculating system. Carbenoxolone inhibited gluconeogenesis as well as decreased oxygen consumption and stimulated glycolysis from fructose, which is an expected combination of phenomena for decreased mitochondrial ATP formation.