Supplementation with Fetal-Specific Factors Ameliorates Oxidative Liver Damage During Hypothermic Storage and Reperfusion in a Rat Model

Abstract

The search for effective methods of long-term liver hypothermic preservation is one of the most important problems in hepatic transplantation. Biologically active substances contained in fetal tissues may be potent stimulators and regulators of metabolic processes, which can support liver during hypothermic storage and after normothermic reperfusion (HS/NR). The aim of this work was to investigate possible influences of fetal-specific factors (FSF) on liver pro-oxidant/antioxidant status, which frequently becomes disturbed during HS/NR in a rat model. As a source of FSF, human fetal tissue cytosolic fraction was used. At 4 h before liver isolation, FSF or Hank's solution were introduced into rat femoral vein (0.3 mL/100 g of body weight). Livers were subjected to HS at 4°C in sucrose-based solution (SBS) for 1 or 24 h, followed by NR for 60 min in vitro. After 1 and 24 h HS, FSF supplementation caused the normalization of hepatic thiobarbituric acid-reactive substances (TBARS) and their accumulation during induction compared with the control group. FSF led to complete restoration of the activities of catalase, GSH-Red, and GSH-PO, both after 1 or 24 h HS and NR. G6PDG was affected by FSF only after 1 h HS/60 min NR. During NR after 24 h HS, FSF supplementation decreased AST activity in the perfusate, but had no effect on ALT. Liver ATP content was significantly increased after 1 h HS compared with the untreated group. These data show that FSF supplementation can attenuate liver free-radical damage during HS/NR, possibly by stimulation or regulation of multiple antioxidant enzyme systems using ATP energy.