Suppression of
leukocyte-enhanced cold ischemia/reperfusion injury of liver endothelium with
the benzoquinone antioxidant idebenone.
Schutz E, Wieland E, Hensel A, Niedmann PD,
Dreiss A, Armstrong
VW, Schuff-Werner P, Oellerich M.
Abteilung Klinische Chemie,
Georg-August-Universitat, Gottingen, Germany. eschuetz@med.uni-goettingen.de
Clin Biochem 1997 Dec;30(8):619-24
Abstract
OBJECTIVE: Despite the large body
of evidence for a major role of neutrophils and oxidant stress, the exact
pathogenesis of the early ischemia/reperfusion injury after cold preservation
of the liver is not well understood. The potential benefit of an antioxidant
on metabolic liver function during reperfusion has been demonstrated in
several studies.
MATERIALS AND METHODS: We describe
a cold storage/reperfusion damage model with isolated perfused pig livers,
where the effects of neutrophils and idebenone, a recently developed
benzoquinone antioxidant, were studied. The integrity of sinusoidal endothelial
cells (SEC) was estimated by hyaluronic acid concentration in perfusate and
the expression of endothelial constitutive nitric oxide synthase (ecNOS) after
reperfusion and compared to lipid peroxidation and antioxidant content.
RESULTS: Hyaluronic acid displayed
the highest levels and ecNOS mRNA was most depressed in livers reperfused with
neutrophils after 20 h cold storage; this was accompanied by an increase in
lipid peroxidation (TBARS) and a breakdown of endogenous lipophilic
antioxidants (alpha-tocopherol and coenzyme Q-10). These effects were
attenuated, when neutrophils were excluded from reperfusion and almost
completely abolished by the addition of 200 mumol/L idebenone.
CONCLUSIONS: These data suggest
that a leukocyte-mediated damage based on reactive oxygen species markedly
contributes to the reperfusion injury of SEC after cold preservation of the
liver. Therefore, the presence of effective antioxidants in the early
reperfusion phase may be beneficial for liver graft integrity.
