The action of extracellular NAD+ in the liver of healthy and tumor-bearing rats: model analysis of the tumor-induced modified response.
The chronic inflammatory state induced by cancer is expected to affect the actions of extracellular NAD(+) in the liver because these are largely mediated by eicosanoids. Under this assumption the present work was planned to investigate the influence of the Walker-256 tumor on the action of extracellular NAD(+) on metabolism and hemodynamics in the perfused rat liver. The experiments were done with livers from healthy and tumor-bearing rats with measurements of gluconeogenesis from lactate, pyruvate production, oxygen consumption and portal pressure. A model describing the biphasic effects of NAD(+) was proposed as an auxiliary worktool for interpretation. The Walker-256 tumor modified the responses of metabolism to extracellular NAD(+) by delaying the peak of maximal responses and by prolonging the inhibitory effects. The transient increase in portal perfusion pressure caused by NAD(+) was enhanced and delayed. The model was constructed assuming the mediation of a down-regulator (inhibition), an up-regulator (stimulation) and receptor dessensitization. Analysis suggested that the productions of both the down- and up-regulators were substantially increased and delayed in time in the tumor-bearing condition. Since the regulators are probably eicosanoids, this analysis is consistent with the increased capacity of producing these agents in the chronic inflammatory state induced by cancer.
de Sá-Nakanishi
Anacharis Babeto
AB
Laboratory of Liver Metabolism, University of Maringá, 87020900 Maringá, Brazil.
Bracht
Fabrício
F
Yamamoto
Nair Seiko
NS
Padilha
Fábio
F
Kelmer-Bracht
Ana Maria
AM
Bracht
Adelar
A
D000818:Animals; D002100:Cachexia / Q000209:etiology / Q000378:metabolism; D002279:Carcinoma 256, Walker / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D015777:Eicosanoids / Q000502:physiology; D045604:Extracellular Fluid / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D006439:Hemodynamics; D007213:Indomethacin / Q000494:pharmacology; D019344:Lactic Acid / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D009243:NAD / Q000502:physiology*; D010101:Oxygen Consumption; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D019289:Pyruvic Acid / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D015777:Eicosanoids; D011500:Protein Synthesis Inhibitors; D009243:NAD; D019344:Lactic Acid; D019289:Pyruvic Acid; D005947:Glucose; D007213:Indomethacin