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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.

Hesperidin (HDN) has been reported to have hydrogen radical- and hydrogen peroxide-removal activities and to serve an antioxidant role in biological systems. However, whether HDN protects hepatocytes (HCs) against hypoxia/reoxygenation (H/R)-induced injury remains unknown. The present study aimed to explore the role of HDN in H/R-induced injury. HCs were isolated and cultured under H/R conditions with or without HDN treatment. HC damage was markedly induced under H/R, as indicated by cell viability, supernatant lactate dehydrogenase levels and alanine aminotransferase levels; however, HDN treatment significantly reversed HC injury. Oxidative stress markers (malondialdehyde, superoxide dismutase, glutathioneand reactive oxygen species) were increased markedly during H/R in HCs; however, this effect was significantly attenuated after exposure to HDN. Compared with those of the control group, the mRNA expression levels of IL-6 and TNF-α in HCs and the concentrations of IL-6 and TNF-α in the supernatants increased significantly following H/R, and HDN significantly ameliorated these effects. Western blotting demonstrated that microtubule-associated protein 1 light chain 3α (MAP1LC3A, also known as LC3) and Beclin-1 protein expression levels increased, while sequestosome 1 levels decreased during H/R following exposure to HDN. The number of GFP-LC3 puncta in HCs following exposure to HDN was increased compared with that observed in HCs without HDN exposure under the H/R conditions after bafilomycin A1 treatment. In summary, the present study demonstrated that HDN attenuated HC oxidative stress and inflammatory responses while enhancing autophagy during H/R. HDN may have a potential protective effect on HCs during H/R-induced injury. [ABSTRACT FROM AUTHOR]