RESUMO
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.
Assuntos
Fígado/efeitos dos fármacos , Fígado/metabolismo , Ácido Oxálico/farmacologia , Alanina/metabolismo , Animais , Ácido Ascórbico/farmacologia , Gluconeogênese/efeitos dos fármacos , Glicólise/efeitos dos fármacos , Técnicas In Vitro , Cinética , Ácido Láctico/biossíntese , Glicogênio Hepático/biossíntese , Masculino , Ácido Oxálico/administração & dosagem , Ácido Oxálico/metabolismo , Consumo de Oxigênio/efeitos dos fármacos , Perfusão , Ácido Pirúvico/metabolismo , Ratos , Ratos WistarRESUMO
Several non-steroidal anti-inflammatories increase glycogenolysis and are also able to affect intracellular Ca2+ channels. In the perfused liver, glycogenolysis stimulation is often associated with a transient Ca2+ efflux, which occurs immediately after the introduction of the glycogenolytic agonist. The purpose of this work was to verify if the introduction of non-steroidal anti-inflammatories also stimulates Ca2+ efflux. Rat livers were pre-loaded with 45Ca2+ in a recirculating system. The anti-inflammatory drugs diclofenac and niflumate were infused 10 minutes after restoration of the once-through perfusion. Glycogenolysis and oxygen uptake stimulation caused by these compounds was not accompanied by any increment in 45Ca2+ release. Subsequent infusion of vasopressin greatly stimulated 45Ca2+ efflux, denoting that the intracellular Ca2+ pools had not been depleted. These results corroborate previous results suggesting that Ca2+ is not involved in glycogenolysis stimulation caused by non-steroidal anti-inflammatories.