Inhalation of high concentrations of hydrogen ameliorates liver ischemia/reperfusion injury through A2A receptor mediated PI3K-Akt pathway
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DOI:
10.1016/j.bcp.2017.02.003
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Abstract:
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.
| Publish Year | 2017 |
|---|---|
| Country | China |
| Rank | Positive |
| Journal | Biochemical Pharmacology |
| Primary Topic | Liver |
| Secondary Topic | Surgery/Transplantation |
| Model | Mouse |
| Tertiary Topic | Ischemia-Reperfusion Injury |
| Vehicle | Gas |
| pH | N/A |
| Application | Inhalation |
| Comparison | |
| Complement |