Rongjia Zhang1, Ling Zhang2, Anatol Manaenko3, Zhouheng Ye1, Wenwu Liu4, Xuejun Sun5. 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.
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.
Authors: Mohamed Bejaoui; Eirini Pantazi; Emma Folch-Puy; Arnau Panisello; María Calvo; Gianfranco Pasut; Antoni Rimola; Miquel Navasa; René Adam; Joan Roselló-Catafau Journal: Biomed Res Int Date: 2015-10-12 Impact factor: 3.411
Authors: Esther M Verhaag; Manon Buist-Homan; Martijn Koehorst; Albert K Groen; Han Moshage; Klaas Nico Faber Journal: PLoS One Date: 2016-03-07 Impact factor: 3.240