title: Effect of specific activation of γ-aminobutyric acid receptor in vivo on oxidative stress-induced damage after extended hepatectomy.
abstract: OBJECTIVE
  γ-Aminobutyric acid (GABA) is a multifunctional molecule with various physiological effects throughout the body. The regulation of GABA receptor (GABAR) plays a key role in reducing the damage mediated by oxidative stress (OS). Extended hepatectomy causes fatal OS-induced injury in the liver remnant. We aimed to investigate the effect of a GABAR agonist in extended hepatectomy.
  
  
  METHODS
  Saline or a GABAR agonist (43.56 nmol/g bodyweight of muscimol) was administrated intravenously at 4 h preoperatively. C57BL/6 mice were divided into three groups: laparotomy only, 90% hepatectomy with saline and 90% hepatectomy with a GABAR agonist. Liver samples were obtained at 6 h after surgery.
  
  
  RESULTS
  Survival curves were prolonged by the GABAR agonist. Histopathological findings and biochemical profiles showed that the GABAR agonist reduced liver damage. Immunohistological assessment demonstrated that the GABAR agonist prevented apoptotic induction. As shown by 4-hydroxynonenal, which reflects OS-induced damage, 90% hepatectomy caused OS and the GABAR agonist reduced OS. We measured ataxia-telangiectasia mutated kinase (ATM), H2AX, Akt and free radical scavenging enzymes because they may be affected by GABAR regulation, and found that Akt was greatly decreased after 90% hepatectomy, but it recovered with the GABAR agonist.
  
  
  CONCLUSIONS
  GABAR is activated by a specific agonist in the liver in vivo. This activation reduces OS-mediated damage after extended hepatectomy in vivo, and the mechanism via an Akt-dependent pathway may be a key.
authors.affiliation: Department of Neuroscience             Division of Transplant Surgery, Department of Transplantation, Mayo Clinic in Florida, Jacksonville, Florida, USA             Division of Hepato-Biliary-Pancreatic, Transplant and Pediatric Surgery, Department of Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Lindsay B
authors.initials: LB
authors.lastname: Gardner
authors.forename: Tomohide
authors.initials: T
authors.lastname: Hori
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.forename: Ann-Marie T
authors.initials: AM
authors.lastname: Baine
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Hata
authors.forename: Shinji
authors.initials: S
authors.lastname: Uemoto
authors.forename: Justin H
authors.initials: JH
authors.lastname: Nguyen