N-acetylcysteine protects hepatocytes from hypoxia-related cell injury

  • Aim of the study: Hepatocyte transplantation has been discussed as an alternative to liver transplantation in selected cases of acute and chronic liver failure and metabolic diseases. Immediately after infusion of hepatocytes, hypoxia-related cell injury is inevitable. N-acetylcysteine (NAC) has been suggested to attenuate hypoxic damage. This study’s objective was to evaluate NAC’s protective effect in a model of hypoxia-related hepatocyte injury. Material and methods: HepG2 cells were used as a model for hepatocytes and were cultured under standardized hypoxia or normoxia for 24 hours with or without NAC. Growth kinetics were monitored using trypan blue staining. The activation of apoptotic pathways was measured using quantitative real-time PCR for Bcl-2/Bax and p53. The proportions of vital, apoptotic and necrotic cells were verified by fluorescence activated cell sorting using annexin V-labelling. The expression of hypoxia inducible factor 1 (HIF-1) was measured indirectly using its downstream target vascular endothelial growth factor A (VEGF-A). Results: After NAC, cell proliferation increased under both hypoxia and normoxia by 528% and 320% (p < 0.05), while VEGF-A expression decreased under normoxia by 67% and 37% (p < 0.05). Compared to cells treated without NAC under hypoxia, the Bcl-2/Bax ratio increased significantly in cells treated with NAC. This finding was confirmed by an increased number of vital cells in FACS analysis. Conclusions: NAC protects hepatocytes from hypoxic injury and ultimately activates anti-apoptotic pathways.

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Author:Jan Heil, Daniel Schultze, Peter Schemmer, Helge Bruns
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/30603674
Parent Title (English):Clinical and experimental hepatology
Place of publication:Poznań
Document Type:Article
Year of Completion:2018
Date of first Publication:2018/12/03
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2019/01/10
Tag:HepG2; N-acetylcysteine; hepatocyte transplantation; hypoxia
Page Number:7
First Page:260
Last Page:266
This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) License, allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung-Keine kommerzielle Nutzung-Weitergabe unter gleichen Bedingungen