RT Journal Article
SR Electronic
T1 Acetazolamide Protects Steatotic Liver Grafts against Cold Ischemia Reperfusion Injury
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP jpet.115.225177
DO 10.1124/jpet.115.225177
A1 Mohamed Bejaoui
A1 Eirini Pantazi
A1 Viviana De Luca
A1 Arnau Panisello
A1 Emma Folch-Puy
A1 Anna Serafin
A1 Clemente Capasso
A1 Claudiu T Supuran
A1 Joan Rosello-Catafau
YR 2015
UL http://jpet.aspetjournals.org/content/early/2015/09/08/jpet.115.225177.abstract
AB Ischemia reperfusion injury (IRI) is a primary concern in liver transplantation especially when steatosis is present. Acetazolamide (AZ), a specific carbonic anhydrases (CAs) 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 rats livers were preserved in Institut Georges Lopez (IGL-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 (eNOS), mitogen activated protein kinases (MAPKs) family, hypoxic inductible factor 1 alpha (HIF-1α) and erythropoietin (Epo)). We demonstrated that AZ administration protects efficiently steatotic liver against cold IRI. AZ protection was associated with better function, decreased vascular resistance and activation of eNOS. This was consistent with an effective MAPKs inactivation. Finally, no effect on HIF-1α/Epo pathway was observed. The present study demonstrated that AZ administration is a suitable pharmacological strategy for preserving fatty liver grafts against cold IRI