Metabolic effects of oxalate in the perfused rat liver.

The effects of oxalate on the metabolism of the isolated perfused rat liver were investigated. The main purpose was to verify if oxalate is also active in intact organs as demonstrated in isolated cells. The results revealed that the action of oxalate in the perfused liver resembles only partially that observed in isolated hepatocytes. In the perfused liver, oxalate inhibited gluconeogenesis from alanine, pyruvate and lactate, inhibited glycolysis and stimulated glycogenolysis. These observations confirm previous measurements with isolated hepatocytes. However, additional effects, not observed in isolated hepatocytes, were found. In the perfused liver, oxalate stimulated glucose production from dihydroxyacetone, glycerol or sorbitol. Moreover, the effects of oxalate in the perfused rat liver occurred at concentrations well above those reported for isolated hepatocytes, revealing that the compound is less toxic in the intact tissue. In vivo, the metabolic effects reported here can only be expected to occur at supra-physiological concentrations of oxalate, as in the case of a chronic renal failure.

The sensitivity of glycogenolysis to glucagon, epinephrine and cyanide in livers from rats in different metabolic conditions.

The action of glucagon, epinephrine and cyanide on hepatic glycogen catabolism in meal-fed rats and the corresponding controls was investigated using the isolated perfused liver. The amounts of glycogen catabolites (glucose, L-lactate and pyruvate) released were correlated with the glycogen content of the livers at the different times after feeding. Irrespective of the metabolic condition, the sensitivity of glycogenolysis to glucagon was roughly proportional to the glycogen content of the livers. However, glycogenolysis in livers from meal-fed rats was less sensitive to epinephrine and cyanide. The difference between meal-fed and controls (ad libitum-fed) was particularly pronounced at 22 hours after feeding. It was concluded that resistance to hepatic glycogen depletion in meal-fed rats during the fasting period may be, partly at least, the consequence of a reduced sensitivity of glycogenolysis to epinephrine and to situations of reduced rates of oxidative phosphorylation.

Effects of the nonsteroidal anti-inflammatory drug mefenamic acid on energy metabolism in the perfused rat liver.

The action of mefenamic acid, a nonsteroidal anti-inflammatory drug, on energy metabolism in the isolated perfused rat liver was investigated. Mefenamic acid in the range between 0.1 and 1.0 mM was infused to livers from well-fed rats and from 24-hr fasted rats. The former were perfused with substrate-free Krebs/Henseleit-bicarbonate buffer, allowing the measurement of glycogenolysis and glycolysis from endogenous glycogen. The livers from 24-hr fasted rats, on the other hand, were perfused with Krebs/Henseleit-bicarbonate buffer containing fructose, thus allowing the measurement of fructolysis and glucose synthesis. Oxygen consumption was measured in both cases. When present in the range between 0.1 and 0.5 mM, mefenamic acid increased glycolysis, oxygen uptake, glycogenolysis and fructolysis. Higher concentrations, depending on the perfusion conditions, were inhibitory. Glucose production from exogenous fructose, on the other hand, was inhibited at low mefenamic acid concentrations. In general terms, the effects of mefenamic acid on energy metabolism seemed to be the primary consequence of its uncoupling action on the respiratory chain. This conclusion is supported mainly by the opposite effects on glucose synthesis (inhibition) and oxygen consumption (activation). The intracellular concentration of mefenamic acid is much higher than the extracellular one, a phenomenon which may represent binding to intracellular membrane or proteins.

Influence of zearalenone on some metabolic pathways of the rat liver.

Zearalenone, a natural product isolated from Fusarium graminearum, has anabolic properties and affects glycogen catabolism in the rat liver. In the isolated perfused liver, L-lactate production, glucose release from endogenous glycogen and oxygen uptake are increased upon infusion of the compound. Fructose metabolism is only slightly affected by zearalenone, except for the transformation of fructose into glucose which is decreased. The action of zearalenone seems to be related to the amount of drug retained by the liver rather than to the concentration in the perfusion fluid.

Influence of zearalenone on some metabolic pathways of the rat liver

Zearali, a natural product isolated from Fusarium granunearum, has anabolic properties and effects glycogen catabolism in the rat liver. In the isolated perfused liver, L-lactate production, glucose release from endogenous glycogen and oxygen uptake are increased upon infusion of the compound. Fructose metabolism is only slightly affected by zearalenone, except for the transformation of fructose intoglucose which is decreased. The actiohn of zearalenone seems to be related to the amount of drug retained by the liver rather than to the concentration in the perfusion fluid

Effect of steviol and its structural analogues on glucose production and oxygen uptake in rat renal tubules.

The effect of several natural products of Stevia rebaudiana on glucose production and oxygen uptake in rat renal cortical tubules was investigated. Steviol, isosteviol and glucosilsteviol decreased glucose production and inhibited oxygen uptake. The sweet principle stevioside, and steviolbioside, however, were without effect on gluconeogenesis and oxygen uptake.