Abstract
Ischemia reperfusion injury (IRI) is a primary concern in liver transplantation, especially when steatosis is present. Acetazolamide (AZ), a specific carbonic anhydrase (CA) inhibitor, has been suggested to protect against hypoxia. Here, we hypothesized that AZ administration could be efficient to protect fatty livers against cold IRI. Obese Zucker rat livers were preserved in Institut Georges Lopez-1 storage solution for 24 hours at 4°C and ex vivo perfused for 2 hours at 37°C. Alternatively, rats were also treated with intravenous injection of AZ (30 mg/kg) before liver recovery. Liver injury, hepatic function, and vascular resistance were determined. CA II protein levels and CA hydratase activity were assessed as well as other parameters involved in IRI (endothelial nitric oxide synthase, mitogen activated protein kinase family, hypoxic inducible factor 1 alpha, and erythropoietin). We demonstrated that AZ administration efficiently protects the steatotic liver against cold IRI. AZ protection was associated with better function, decreased vascular resistance, and activation of endothelial nitric oxide synthase. This was consistent with an effective mitogen activated protein kinase inactivation. Finally, no effect on the hypoxic inductible factor 1 alpha/erythropoietin pathway was observed. The present study demonstrated that AZ administration is a suitable pharmacological strategy for preserving fatty liver grafts against cold IRI.
Footnotes
- Received April 15, 2015.
- Accepted August 26, 2015.
This work was supported by the Ministerio de Economía y Competividad (Spain) through the “Fondo de Investigaciones Sanitarias” (FIS) [Grant PI12/00519].
This work has been presented by Bejaoui M et al. as follows: 14th Annual Congress of the French-Speaking Society of Transplantation; 2–5 Dec 2014; Caen, France and in the 13th Congress of the Catalan Society of Transplantation, 18–20 Mar 2015; Barcelona, Spain. Catalan Society of Transplantation, Barcelona, Spain.
- Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics
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