Multinuclear NMR investigations on the metabolic recovery of the isolated perfused mouse liver after cold preservation.
This paper describes multinuclear NMR investigations on the isolated perfused mouse liver to optimize its recovery after cold preservation and normothermic reperfusion. The recovery of livers from fed is better than that from 24 h fasted animals. This better recovery is not due to a higher glycogen content before cold preservation. The recovery of livers from fasted animals is specifically enhanced by the presence of 8 mM alanine in the rinsing solution after cold preservation and in the perfusate of reperfusion. This property is not due to the ability of alanine to compensate for the lack of endogenous substrates since the amount, before cold preservation, of these substrates, is not significantly different in livers from fed and fasted animals. Furthermore, the beneficial effect of alanine is not due to an enhancement of the pyruvate dehydrogenase (PDH) activity in livers from fasted animals. In fact these livers have indeed a smaller PDH activity than the livers from fed animals but dichloroacetate, a known PDH activator has a rather deleterious effect on the recovery of fed and fasted livers. Furthermore alanine protects the fasted livers against this effect. So the beneficial effect of alanine should be due to other causes. Furthermore, we have found on a parallel model of rat isolated perfused liver, that the recovery of steatotic livers which is lower than that of normal fed livers is enhanced by a known vasodilator, pentoxifylin but not by alanine. So alanine does not either play its role through its action on microcirculation. The interaction of alanine with some membrane sodium transporters like that already reported for another protective aminoacid, glycine, is thus possible. A novel NMR method of (23)Na observation in living cells or organs should be of great interest to investigate this hypothesis.
Dimicoli
Jean-Luc
JL
Unité 350 Inserm, Institut Curie, Bâtiment 112, Centre Universitaire, 91405 cedex Orsay, France. jean-luc.dimicoli@curie.u-psud.fr
Patry
Jacqueline
J
Blouquit
Yves
Y
Nedelec
Jean-François
JF
Adam
René
R
D000409:Alanine / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D002247:Carbon Isotopes; D015925:Cryopreservation / Q000379:methods*; D003999:Dichloroacetic Acid / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005215:Fasting / Q000502:physiology*; D007658:Ketone Oxidoreductases / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008112:Liver Glycogen / Q000378:metabolism; D008297:Male; D051379:Mice; D008833:Microcirculation; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D010477:Perfusion; D020127:Recovery of Function / Q000502:physiology; D014280:Triglycerides / Q000378:metabolism
D002247:Carbon Isotopes; D008112:Liver Glycogen; D014280:Triglycerides; D003999:Dichloroacetic Acid; D007658:Ketone Oxidoreductases; C053164:pyruvate dehydrogenase (NADP+); D000409:Alanine