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. 2022 Dec;10(6):e01027.
doi: 10.1002/prp2.1027.

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

Agustin Vintimilla Moscoso  1 , Estela Regina Ramos Figueira  1   2 , Joel Avancini Rocha-Filho  1   3 , Martin Urner  4   5 , Cinthia Lanchotte  1 , Jose Jukemura  1   2 , Jorge Luiz Saraiva Ximenes  1 , Sergio Carlos Nahas  2 , Luiz Augusto Carneiro D'Albuquerque  1   6 , Flavio Henrique Ferreira Galvao  1   6
Affiliations

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

Agustin Vintimilla Moscoso et al. Pharmacol Res Perspect. 2022 Dec.

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.

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Conflict of interest statement

The authors declare there are no conflicts of interest.

Figures

FIGURE 1
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
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
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