Hepatic preservation, liposomally entrapped adenosine triphosphate and nitric oxide production: a study of energy state and protein metabolism in the cold-stored rat liver.
BACKGROUND
Liposomally entrapped adenosine triphosphate (ATP) has been demonstrated to improve energy state and function of the cold-stored liver. The increased nitrite release associated with liposome administration led us to investigate the interactions between liposome supply and nitric oxide (NO) production through the use of L-NAME, a non-selective inhibitor of NO synthesis.


METHODS
Twenty-four livers from fasted rats were stored for 18 h at +4 degrees C in University of Wisconsin solution directly (control group) or after infusion with ATP-containing liposomes (Lip-ATP), L-NAME (L-NAME) or both (Lip-ATP-L-NAME). Metabolic fluxes, cell volume and energy state were studied during reperfusion.


RESULTS
After storage, nitrite release was increased by 61% in the Lip-ATP group, markedly decreased in the Lip-ATP-L-NAME group and almost abolished in the L-NAME group. The ATP content was increased by 20% in the Lip-ATP group (P < 0.05 versus control) and on reperfusion this was associated with an increase in cell volume (17%; P < 0.05) and a decrease in branched-chain amino acid release (21%; P < 0.01). The simultaneous addition of L-NAME did not affect these results, but induced a large (6-fold) increase in glucose production, possibly related to the metabolism of glycerol supplied by the liposomes. In the L-NAME group, global amino acid release was 50% lower and was associated with a dramatic decrease in urea production while the energy state deteriorated rapidly.


CONCLUSIONS
The improvement in energy state and anabolic cell swelling induced by ATP-containing liposomes seems to be independent of NO synthesis. On the other hand, inhibition of NO synthesis appears to exert a detrimental effect on the liver, presumably through the decrease in hepatic energy content.
Neveux
N
N
Laboratoire de Biochimie A, Hĵpital de l'Hĵtel Dieu, AP-HP, Paris, France. nathalie.neveux@htd.ap_hop_paris.fr
De Bandt
J P
JP
Chaumeil
J C
JC
Cynober
L
L
D000255:Adenosine Triphosphate / Q000008:administration & dosage* / Q000378:metabolism; D000818:Animals; D015925:Cryopreservation; D004734:Energy Metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D008081:Liposomes; D008099:Liver / Q000378:metabolism; D008111:Liver Function Tests; D008297:Male; D023421:Models, Animal; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D009926:Organ Preservation / Q000379:methods*; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014508:Urea / Q000378:metabolism
D004791:Enzyme Inhibitors; D008081:Liposomes; D011506:Proteins; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D014508:Urea; D005947:Glucose; D019331:NG-Nitroarginine Methyl Ester