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J Hepatol. 2014 Nov;61(5):1048-55. doi: 10.1016/j.jhep.2014.06.020. Epub 2014 Jun 24.

Helium preconditioning protects mouse liver against ischemia and reperfusion injury through the PI3K/Akt pathway.

Author information

1
Department of Diving Medicine, Second Military Medical University, Shanghai, China.
2
Department of Medical Genetics, Second Military Medical University, Shanghai, China.
3
Department of Physiology and Pharmacology, Loma Linda University Medical Center, Loma Linda, CA, USA.
4
Department of Diving Medicine, Second Military Medical University, Shanghai, China. Electronic address: liuwenwu1980@hotmail.com.
5
Department of Diving Medicine, Second Military Medical University, Shanghai, China. Electronic address: sunxjk@hotmail.com.

Abstract

BACKGROUND & AIMS:

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.

KEYWORDS:

Air gap; Helium preconditioning; Liver I/R injury; PI3K/Akt

PMID:
24972044
DOI:
10.1016/j.jhep.2014.06.020
[Indexed for MEDLINE]

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