Potential protective effect of hesperidin on hypoxia/reoxygenation-induced hepatocyte injury

Shilai Li; Jijin Zhu; Ling Pan; Peiqi Wan; Quanlin Qin; Daqing Luo; Wenhui Pan; Yuqing Wei; Yansong Xu; Liming Shang; Xinping Ye

doi:10.3892/etm.2021.10196

Potential protective effect of hesperidin on hypoxia/reoxygenation-induced hepatocyte injury

Exp Ther Med. 2021 Jul;22(1):764. doi: 10.3892/etm.2021.10196. Epub 2021 May 13.

Authors

Shilai Li¹, Jijin Zhu¹, Ling Pan², Peiqi Wan³, Quanlin Qin¹, Daqing Luo¹, Wenhui Pan¹, Yuqing Wei¹, Yansong Xu¹, Liming Shang⁴, Xinping Ye⁴

Affiliations

¹ Department of Emergency, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
² Department of Nephrology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
³ Department of Infectious Diseases, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
⁴ Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.

Abstract

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.

Keywords: autophagy; hepatocyte; hesperidin; hypoxia/reoxygenation; oxidative stress.

Grants and funding

Funding: This study was supported by The Young Teachers' Basic Ability Improvement in Guangxi University Project (grant no. 2019KY0108), the National Natural Science Foundation of China (grant no. 81960358),Talents Sub-Highland of Emergency and Medical Rescue of Guangxi Province in China (grant no. GXJZ201405), Health Commission of Guangxi (grant no. Z2016289), the Guangxi Natural Science Foundation (grant nos. 2018JJB140279 and 2020GXNSFAA159127), Guangxi Key Laboratory for the Prevention and Control of Viral Hepatitis (grant no. GXCDCKL201902) and the Medical Excellence Award funded by the Creative Research Development Grant from the First Affiliated Hospital of Guangxi Medical University (grant no. 2017-11-7).