Resveratrol biotransformation and actions on the liver metabolism of healthy and arthritic rats

Aims: to investigate the effects of resveratrol on glycogen catabolism and gluconeogenesis in perfused livers of healthy and arthritic rats. The actions of resveratrol-3-O-glucuronide (R3G) and the biotransformation of resveratrol into R3G was further evaluated in the livers.

Main methods: arthritis was induced with Freund's Adjuvant. Resveratrol at concentrations of 10, 25, 50, 100 and 200 μM and 200 μM R3G were introduced in perfused livers. Resveratrol and metabolites were measured in the outflowing perfusate. Respiration of isolated mitochondria and activity of gluconeogenic Enzymes were also evaluated in the livers.

Key findings: resveratrol inhibited glycogen catabolism when infused at concentrations above 50 μM and gluconeogenesis even at 10 μM in both healthy and arthritic rat livers, but more sensitive in these latter. Resveratrol above 100 μM inhibited ADP-stimulated respiration and the activities of NADH- and succinate-oxidases in mitochondria, which were partially responsible for gluconeogenesis inhibition. Pyruvate carboxylase activity was inhibited by 25 μM resveratrol and should inhibit gluconeogenesis already at low concentrations. Resveratrol was significantly metabolized to R3G in healthy rat livers, however, R3G formation was lower in arthritic rat livers. The latter must be in part a consequence of a lower glucose disposal for glucuronidation. When compared to resveratrol, R3G inhibited gluconeogenesis in a lower extension and glycogen catabolism in a higher extension.

Significance: the effects of resveratrol and R3G tended to be transitory and existed only when the resveratrol is present in the organ, however, they should be considered because significant serum concentrations of both are found after oral ingestion of resveratrol.

Gluconeogenesis; Liver metabolism; Pyruvate carboxylase; Resveratrol; Resveratrol glucuronide; Rheumatoid arthritis.