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Effect of apoE/ATP-containing liposomes on hepatic energy state

Authors


Dr JP De Bandt, Laboratoire de Biologie de la Nutrition, Faculté de Pharmacie, 4, avenue de l'Observatoire, 75270 Paris Cedex 06, France.
Tel: 33/(0)1 53 73 99 53
Fax: 33/(0)1 53 73 99 52
e-mail: debandt@pharmacie.univ-paris5.fr

Abstract:

Background/Aims: 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 μmol)-containing liposomes (ATP-Lip, n=6) or apoE/ATP-containing liposomes (0.8 or 8 mg 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.

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