Hexafluoroisopropanol decreases liver ischemia-reperfusion injury by downregulation of high mobility group box-1 protein

Abstract

Liver ischemia-reperfusion (IR) injury is associated with poor outcome after liver transplantation and liver resections. Hexafluoroisopropanol (HFIP) is a tri-fluorinated metabolites of volatile anesthetics and has modulatory effects on inflammation that have been observed mainly in cell culture experiments. In this survey, we investigated the effects of HFIP in a rat model of normothermic hepatic ischemia-reperfusion injury. Twenty-four male Wistar rats were randomized into three groups: (1) control in which animals were submitted to 30 min of partial liver ischemia with resection of non-ischemic liver lobes immediate after reperfusion, (2) pre-ischemia (PI) group in which animals received intravenous HFIP (67 mg/kg) 5 min before liver ischemia, and (3) pre-reperfusion (PR) group in which animals received intravenous HFIP (67 mg/kg) 5 min before reperfusion. Four hours after reperfusion, all animals were euthanized for sample collection. Aspartate and alanine transaminases, glucose, and high mobility group box-1 (HMGB-1) protein concentrations showed a significant decreased, and malondialdehyde was increased in the PR group compared with control and PI groups. Interleukin 6 (IL-6) was increased in the PI group compared with control and PR groups. IL-10 and -12 were increased in the PR and PI groups, respectively, when compared with the control group. Glucose decreased in the PR when compared with the control group. Post-conditioning with HFIP led to a decrease in hepatocellular injury and was associated with a downregulation of HMGB-1. The HFIP resulted in a better control of inflammatory response to ischemia-reperfusion even without causing a reduction in oxidative stress.

Keywords: hexafluoroisopropanol; ischemia; ischemic postconditioning; ischemic preconditioning; liver; reperfusion injury.

FIGURE 1

Aspartate transaminase, AST (A); alanine transferase, ALT (B); high mobility group box‐1 protein, HMGB‐1 (C); oxidative stress (D). Groups: control, administration of hexafluoroisopropanol pre‐reperfusion (PR) and pre‐ischemia (PI). Statistical analysis was performed using unpaired Student's t test, n = 8 in each group

FIGURE 2

Mean blood pressure (A). Groups: control, PR (administration of hexafluoroisopropanol pre‐reperfusion), and PI (pre‐ischemia). Portal venous flow (B) evaluated before ischemia (base), 5 min after ischemia (5 min Post‐isch), and 4 hafter reperfusion (4 h Post‐rep). *p < .05 compared with other groups. Statistical analysis was performed using unpaired Student's t test, n = 8 in each group