Effect of specific activation of γ-aminobutyric acid receptor in vivo on oxidative stress-induced damage after extended hepatectomy.

Hepatology Research : the Official Journal of the Japan Society of Hepatology
Lindsay B GardnerJustin H Nguyen

Abstract

  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.   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.   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 greatl...Continue Reading

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Citations

Oct 18, 2014·Molecular Human Reproduction·Kaoru KawasakiIkuo Konishi
Jun 14, 2016·Scientific Reports·Mei-Lin ShenDong Chuan Wu
Feb 28, 2014·World Journal of Hepatology·Tomohide HoriJustin H Nguyen
Aug 26, 2018·Cancers·Jomnarong LertsuwanJutamaad Satayavivad
Jul 9, 2017·Biochemical and Biophysical Research Communications·Haoyue YangPengcheng Li

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