17 June 2013
Pretreatment of liver grafts in vivo by γ-aminobutyric acid receptor regulation reduces cold ischemia/warm reperfusion injury in rat
Tomohide HoriBCDEFG, Lindsay B. GardnerBCDF, Toshiyuki HataBCDF, Feng ChenBDF, Ann-Marie T. BaineBDF, Shinji UemotoDG, Justin H. NguyenADFGDOI: 10.12659/AOT.883955
Ann Transplant 2013; 18:299-313
Abstract
BACKGROUND: Gamma-aminobutyric acid (GABA) is found throughout the body. The regulation of GABA receptor (GABAR) reduces oxidative stress (OS). Ischemia/reperfusion injury after orthotopic liver transplantation (OLT) causes OS-induced graft damage. The effects of GABAR regulation in donors in vivo were investigated.
MATERIAL AND METHODS: Donor rats received saline, a GABAR agonist or GABAR antagonist 4 h before surgery. Recipient rats were divided into four groups according to the donor treatments: laparotomy, OLT with saline, OLT with GABAR agonist and OLT with GABAR antagonist. Histopathological, biochemical and immunohistological examinations were performed at 6, 12 and 24 h after OLT. Protein assays were performed at 6 h after OLT. The 4-hydroxynonenal (4-HNE), ataxia-telangiectasia mutated kinase (ATM), phosphorylated histone H2AX (gammaH2AX), phosphatidylinositol-3 kinase (PI3K), Akt and superoxide dismutase (SOD) were assessed by western blot analysis.
RESULTS: In the univariate analysis, histopathological and biochemical profiles verified that the GABAR agonist reduced graft damage. Immunohistology revealed that the GABAR agonist prevented the induction of apoptosis. Measurement of 4-4-HNE levels confirmed OS-induced damage after OLT, and the GABAR agonist improved this damage. In the gammaH2AX, PI3K, Akt and antioxidant enzymes (SODs), ATM and H2AX were greatly increased after OLT, and were reduced by the GABAR agonist. In the multivariate analyses between multiple groups, histopathological assessment, aspartate aminotransferase level, immunohistological examinations for apoptotic induction and gammaH2AX showed statistical differences.
CONCLUSIONS: A specific agonist demonstrated regulation of GABAR in vivo in the liver. This activation in vivo reduced OS after OLT via the ATM/H2AX pathway.
Keywords: liver, Free Radicals, cold ischemia, warm reperfusion
In Press
08 Mar 2024 : Original article
Association of Coronary Calcium Score on Cardiac PET During Pre-Kidney Transplant Assessment with Persisten...Ann Transplant In Press; DOI: 10.12659/AOT.943532
14 Mar 2024 : Original article
Impact of Blood Products Transfusion on Patients in the Immediate Post-Lung Transplant Period: A Cohort StudyAnn Transplant In Press; DOI: 10.12659/AOT.943652
14 Mar 2024 : Case report
Treatment of Cavernous Transformation of Portal Vein Caused by Hepatic Cystic Echinococcosis Using Ex Vivo ...Ann Transplant In Press; DOI: 10.12659/AOT.942358
15 Mar 2024 : Review article
Approaches and Challenges in the Current Management of Cytomegalovirus in Transplant Recipients: Highlighti...Ann Transplant In Press; DOI: 10.12659/AOT.941185
Most Viewed Current Articles
05 Apr 2022 : Original article
Impact of Statins on Hepatocellular Carcinoma Recurrence After Living-Donor Liver TransplantationDOI :10.12659/AOT.935604
Ann Transplant 2022; 27:e935604
12 Jan 2022 : Original article
Risk Factors for Developing BK Virus-Associated Nephropathy: A Single-Center Retrospective Cohort Study of ...DOI :10.12659/AOT.934738
Ann Transplant 2022; 27:e934738
22 Nov 2022 : Original article
Long-Term Effects of Everolimus-Facilitated Tacrolimus Reduction in Living-Donor Liver Transplant Recipient...DOI :10.12659/AOT.937988
Ann Transplant 2022; 27:e937988
15 Mar 2022 : Case report
Combined Liver, Pancreas-Duodenum, and Kidney Transplantation for Patients with Hepatitis B Cirrhosis, Urem...DOI :10.12659/AOT.935860
Ann Transplant 2022; 27:e935860