Author/Authors :
Helewski, Krzysztof Department of Histology and Embryology - Medical University of Silesia - Zabrze, Poland , Kowalczyk-Ziomek, Grazyna Department of Histology and Embryology - Medical University of Silesia - Zabrze, Poland , Czecior, Eugeniusz Department of ENT - Medical University of Silesia - Zabrze, Poland , Wyrobiec, Grzegorz Department of Histology and Embryology - Medical University of Silesia - Zabrze, Poland , Harabin-Slowinska, Marzena Department of Histology and Embryology - Medical University of Silesia - Zabrze, Poland , Juszko-Piekut, Malgorzata Department of Hygiene - Bioanalysis and Environmental Studies - School of Pharmacy - Medical University of Silesia - Zabrze, Poland , Braczkowska, Bogumila Department of Epidemiology - Medical University of Silesia - Katowice, Poland , Josko, Jadwiga Department of Environmental Medicine and Epidemiology - Medical University of Silesia - Zabrze, Poland
Abstract :
Background: Intermittent clamping (IC) of the portal triad is an effective method of
protecting the liver from ischemia-reperfusion injury (IR). In clinical practice, this
method is employed during a resection, but its mechanism is still not clear.
Objectives: To evaluate the effect of IC on rat liver and determine its mechanisms.
Materials and Methods: Wistar rats were submitted to 60-min IC (cycles of 12-min
clamping followed by 4-min reperfusion), and the samples were collected after 1, 6,
and 72 hrs of reperfusion. We determined the serum activity of alanine aminotransferase
(ALT), and measured the concentration of TNF-α, malondialdehyde (MDA) and
myeloperoxidase (MPO) in liver homogenates. The apoptosis of hepatocytes was evaluated
immunohistochemically.
Results: When compared to the IR rats, the activity of ALT decreased in the IC group
in all periods of observation (the highest decrease of ~48% after 1 hr of reperfusion).
When compared to the IR group, a statistically significant decrease (p < 0.05) in the
TNF-α concentration (~33%) in the IC rats occurred only after 1 hr of reperfusion, and
it was accompanied by a decrease in the MPO concentration after 1 and 6 hrs of reperfusion.
IC reduces the effects of reactive oxygen species (ROS) activity, which has been
confirmed by a statistically significant decrease in MDA concentration by 25%–35% in
all studied periods. The limitation of hepatocytes apoptosis due to IC occurs in the
early (~26%; p < 0.05) and late (~45%; p < 0.01) phases of reperfusion.
Conclusions: The use of IC in early phase of reperfusion brings about a decrease in
TNF-α release, which can be related to liver injury due to neutrophil infiltration and
apoptotic cell reduction. It seems that the reduction of lipid peroxidation may also
limit the liver injury.
Keywords :
Ischemic preconditioning , Acute liver failure , Reperfusion injury , TNF-alpha , Apoptosis