TY - JOUR T1 - Acetazolamide Protects Steatotic Liver Grafts against Cold Ischemia Reperfusion Injury JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 191 LP - 198 DO - 10.1124/jpet.115.225177 VL - 355 IS - 2 AU - Mohamed Bejaoui AU - Eirini Pantazi AU - Viviana De Luca AU - Arnau Panisello AU - Emma Folch-Puy AU - Anna Serafin AU - Clemente Capasso AU - Supuran C. T. AU - Joan Rosselló-Catafau Y1 - 2015/11/01 UR - http://jpet.aspetjournals.org/content/355/2/191.abstract N2 - 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. ER -