title: Helium preconditioning protects mouse liver against ischemia and reperfusion injury through the PI3K/Akt pathway.
abstract: OBJECTIVE
  Hepatic ischemia and reperfusion (I/R) injury is a major complication of liver transplantation, hepatic resection and trauma. Helium preconditioning (HPC) exerts protection against ischemic stress. We investigated potential beneficial effects of HPC on I/R-induced liver injury and investigated mechanisms underlying HPC-induced protection.
  
  
  METHODS
  We employed a model of segmental warm hepatic I/R on BALB/c mice. Serum ALT was measured and livers were analysed by histology, RT-PCR and western blot. HPC was induced by inhalation of a 70% helium/30% oxygen mixture for three 5-min periods, interspersed with three 5-min washout periods by room air. We tested which component of HPC (the helium/air mixture inhalation, the air room gap, or the interaction between these two factors) is protective.
  
  
  RESULTS
  We found that HPC caused a significant increase in Akt phosphorylation in hepatocytes. The HPC-induced Akt phosphorylation resulted in decreased hepatocellular injury and improved survival rate of the treated animals. PI3K inhibitors abolished HPC induced effects. HPC-induced Akt phosphorylation affected expression of its downstream molecules. The effects of HPC on the PI3K/Akt pathway were attenuated by adenosine A2A receptor blockade, but could be re-established by PTEN inhibition. We demonstrated that the interaction of helium/air breathing and air gaps is responsible for the observed effects of HPC.
  
  
  CONCLUSIONS
  HPC may be a promising strategy leading to a decrease in I/R induced liver injury in clinical settings. Additionally, the PI3K/Akt pathway plays an essential role in the protective effects of HPC in hepatic I/R injury.
authors: Department of Diving Medicine, Second Military Medical University, Shanghai, China.
authors: Rongjia
authors: R
authors: Zhang
authors: Department of Medical Genetics, Second Military Medical University, Shanghai, China.
authors: Ling
authors: L
authors: Zhang
authors: Department of Physiology and Pharmacology, Loma Linda University Medical Center, Loma Linda, CA, USA.
authors: Anatol
authors: A
authors: Manaenko
authors: Department of Diving Medicine, Second Military Medical University, Shanghai, China.
authors: Zhouheng
authors: Z
authors: Ye
authors: Department of Diving Medicine, Second Military Medical University, Shanghai, China. Electronic address: liuwenwu1980@hotmail.com.
authors: Wenwu
authors: W
authors: Liu
authors: Department of Diving Medicine, Second Military Medical University, Shanghai, China. Electronic address: sunxjk@hotmail.com.
authors: Xuejun
authors: X
authors: Sun
mesh_terms: D058917:Adenosine A2 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004195:Disease Models, Animal; D006371:Helium / Q000627:therapeutic use*; D019194:Ischemic Preconditioning / Q000379:methods*; D008099:Liver / Q000187:drug effects / Q000293:injuries / Q000378:metabolism; D016031:Liver Transplantation / Q000009:adverse effects / Q000379:methods; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000037:antagonists & inhibitors; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015398:Signal Transduction; D019172:Transplantation Conditioning / Q000379:methods*; D014227:Triazines / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology; D052096:Warm Ischemia
chemical_list: D058917:Adenosine A2 Receptor Antagonists; D016328:NF-kappa B; D014227:Triazines; D014230:Triazoles; C097270:ZM 241385; D006371:Helium; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse
keywords: Air gap; Helium preconditioning; Liver I/R injury; PI3K/Akt