TY - JOUR AB - Hesperidin (HDN) is a bioflavonoid that serves a role as an antioxidant in biological systems. However, although HDN has hydrogen radical‑ and hydrogen peroxide‑removal activities, the role of HDN in liver ischemia/reperfusion (I/R) injury remains unknown. This study aimed to determine the role of HDN in liver I/R injury. Male C57BL/6J wild‑type (WT) mice were subjected to warm partial liver I/R injury. Liver damage was evaluated by measuring serum alanine aminotransferase (ALT) levels, cytokine production, oxidative stress indicators, tissue hematoxylin‑eosin staining and cell death. The Akt signaling pathway was examined to elucidate the underlying mechanisms. HDN had no effect on ALT levels and tissue damage in WT mice without liver I/R injury. However, HDN significantly ameliorated liver I/R injury as measured by serum ALT levels and necrotic tissue areas. HDN decreased malondialdehyde content, but increased the levels of superoxide dismutase, catalase, glutathione peroxidase and glutathione. In addition, HDN significantly attenuated the mRNA expression levels of TNF‑α, IL‑6 and IL‑1β after liver I/R injury. Furthermore, HDN protected the liver against apoptosis in liver I/R injury by increasing the levels of Bcl‑2 and decreasing the levels of cleaved‑caspase 3. Mechanistically, the levels of phosphorylated Akt were elevated by HDN during liver I/R injury. In addition, HDN could induce Akt activation in hepatocytes in vitro. Most importantly, treatment with the Akt inhibitor LY294002 in WT mice blocked the hepatoprotective effects of HDN in liver I/R injury. In summary, the results of the present study suggested that HDN may protect against liver I/R injury through activating the Akt pathway by ameliorating liver oxidative stress, suppressing inflammation and preventing hepatocyte apoptosis. HDN may be a useful factor for liver injury protection and a potential therapeutic treatment for liver I/R injury in the future. AD - Department of Emergency, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R China Department of Emergency, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R China Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R China AU - Li,Shilai AU - Qin,Quanlin AU - Luo,Daqing AU - Pan,Wenhui AU - Wei,Yuqing  AU - Xu,Yansong AU - Zhu,Jijin AU - Shang,Liming DA - 2020/12/01 DO - 10.3892/mmr.2020.11561 EP - 4530 IS - 6 JO - Mol Med Rep KW - hesperidin liver ischemia/reperfusion injury oxidative stress apoptosis Ak PY - 2020 SN - 1791-2997 1791-3004 SP - 4519 ST - Hesperidin ameliorates liver ischemia/reperfusion injury via activation of the Akt pathway T2 - Molecular Medicine Reports TI - Hesperidin ameliorates liver ischemia/reperfusion injury via activation of the Akt pathway UR - https://doi.org/10.3892/mmr.2020.11561 VL - 22 ER -