Uncoupling protein-2 deficient mice are not protected against warm ischemia/reperfusion injury of the liver.

Background: Uncoupling protein-2 (UCP2) might play an important role in mediating ischemia/reperfusion (I/R) injury due to its function in uncoupling of oxidative phosphorylation and in the proton leak-associated increase of reactive oxygen species (ROS) production. The aim of this study was to elucidate the role of UCP2 in hepatic I/R injury.

Materials And Methods: UCP2 wild type and UCP2 deficient mice were subjected to I/R of the left liver lobe. Sham-operated animals without I/R served as controls. Intravital fluorescence microscopy was used for assessing postischemic microcirculatory dysfunction. Indicators of hepatic inflammatory response, oxidative stress, and bioenergetic status as well as histomorphology were investigated.

Results: Under sham conditions UCP2-/-mice presented slightly but not significantly higher levels of hepatic ATP and energy charge than wild type mice. In addition, they exhibited higher systemic IL-6 levels and intrahepatic leukocyte adherence. After exposure to I/R, the extent of reperfusion injury did not differ between UCP2+/+ and UCP2-/-mice, as indicated by a comparable loss of sinusoidal perfusion, hepatic ATP, and energy charge levels, as well as rise of transaminases and disintegration of liver structures. Intrahepatic leukocyte adherence and plasma IL-6 levels of postischemic UCP2-/-mice still exceeded those of UCP2+/+mice.

Conclusions: UCP2 appears to be of minor relevance for the manifestation and extent of postischemic reperfusion injury in nondiseased livers with the increased ATP availability being counteracted by the higher pro-inflammatory IL-6 levels in UCP2 deficient mice.