H2 inhalation mitigates liver injury via A2A receptor and PI3K-Akt pathwayScientific Research

original title: Inhalation of high concentrations of hydrogen ameliorates liver ischemia/reperfusion injury through A2A receptor mediated PI3K-Akt pathway


He Li, Ouyang Chen, Zhouheng Ye, Rongjia Zhang, Huijun Hu, Ning Zhang, Junlong Guang, Wenwu Liu, Xue Sun

DOI: 10.1016/j.bcp.2017.02.003



Background and aims: This study explored the hepatoprotection of high concentrations of hydrogen (HCH) inhalation in a mouse hepatic ischemia/reperfusion (I/R) injury model and the potential mechanism.

Methods: To explore the role of the PI3K-Akt pathway in the hepatoprotection of HCH, C57BL/6 mice were randomly divided into five groups: Sham, I/R, I/R + HCH, LY294002 (PI3K inhibitor) + I/R + HCH, and LY + I/R groups. Mice received inhalation of 66.7% hydrogen and 33.3% oxygen for 1 h immediately after surgery. LY294002 was intravenously injected at 10 mol/kg. To explore whether PI3K-Akt pathway activation was mediated by the A2A receptor, additional four groups were included: ZM241385 (A2A receptor antagonist) + I/R + HCH, ZM241385 + I/R, bpv(HOpic) (PTEN inhibitor) + I/R, and ZM241385 + bpv + I/R + HCH. Six hours after I/R, serum biochemistry, histological examination, Western blotting, and immunohistochemistry were performed to evaluate the hepatoprotection of HCH and the role of the PI3K-Akt pathway and A2A receptor in this protection.

Results: Liver dysfunction, hepatic pathological injury, infiltration of inflammatory cytokines, and hepatocyte apoptosis were observed after hepatic I/R, accompanied by inhibition of the PI3K-Akt pathway. HCH significantly improved liver function, reduced serum inflammatory cytokines, and inhibited hepatocyte apoptosis, and also induced the PI3K-Akt pathway activation. In the presence of LY294002 or ZM241385, the protective effects of HCH were markedly attenuated, but the effects of ZM241385 were reversed by bpv(HOpic).

Conclusion: Our findings indicate that HCH may protect the liver against I/R injury through the A2A dependent PI3K-Akt pathway.