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Effect of specific activation of γ‐aminobutyric acid receptor in vivo on oxidative stress‐induced damage after extended hepatectomy
Author(s) -
Gardner Lindsay B.,
Hori Tomohide,
Chen Feng,
Baine AnnMarie T.,
Hata Toshiyuki,
Uemoto Shinji,
Nguyen Justin H.
Publication year - 2012
Publication title -
hepatology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.123
H-Index - 75
eISSN - 1872-034X
pISSN - 1386-6346
DOI - 10.1111/j.1872-034x.2012.01030.x
Subject(s) - agonist , hepatectomy , endocrinology , medicine , muscimol , pharmacology , oxidative stress , receptor , surgery , resection
Aim: 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. Conclusion: 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.