Effect of apoE/ATP-containing liposomes on hepatic energy state.
OBJECTIVE
ATP-containing liposomes partially prevent ATP depletion in the cold-stored liver. As hepatocytes can specifically bind apoE, we investigated whether the addition of apoE to large (200 nm) ATP-containing liposomes increases their uptake by the liver and further improves hepatic energy stores.


METHODS
Livers from fasted male Hartley guinea-pigs (231 +/- 3 g) were perfused for 90 min under our standard conditions (Control, n = 6) or after a single bolus addition of plain liposomes (Lip, n = 6), ATP (5 micromol)-containing liposomes (ATP-Lip, n = 6) or apoE/ATP-containing liposomes (0.8 or 8mg apoE/g phospholipids; apoE1-Lip and apoE10-Lip, respectively, n = 6 in each group). Liposome uptake and its impact on energy and nitrogen metabolism were studied.


RESULTS
At its highest concentration, apoE significantly increased liposome uptake (apoE10-Lip: - 9.17 +/- 0.69 vs apoE1-Lip: - 6.18 +/- 0.44 vs ATP-Lip: - 6.40 +/- 0.88 nmol min(-1) g(-1) P < 0.05). This was associated with a significant increase in intrahepatic ATP (apoE10-Lip: 1033 +/- 137 vs apoE1-Lip: 811 +/- 98 and ATP-Lip: 648 +/- 36 nmol g(-1); P < 0.05), which was restored to its level in non-perfused livers. Hepatic viability and nitrogen metabolism were not affected.


CONCLUSIONS
Hepatic ATP content being a key factor in the maintenance of liver graft function, apoE/ATP-containing liposomes should be useful in liver preservation for transplantation.
Chaïb
S
S
Laboratoire de Biologie de la Nutrition EA 2498, Faculté de Pharmacie, Paris, France.
Charrueau
C
C
Neveux
N
N
Nakib
S
S
Chaumeil
J C
JC
Cynober
L
L
De Bandt
J P
JP
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D001057:Apolipoproteins E / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology*; D006085:Graft Survival; D006168:Guinea Pigs; D008081:Liposomes; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D016031:Liver Transplantation; D008297:Male; D010477:Perfusion
D001057:Apolipoproteins E; D008081:Liposomes; D000255:Adenosine Triphosphate