An investigation into the inflammatory properties of tenofovir in HepGโ human liver cells
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Date
2023
Authors
Vazi, Songezo
Journal Title
Journal ISSN
Volume Title
Publisher
University of the Free State
Abstract
๐๐ป๐๐ฟ๐ผ๐ฑ๐๐ฐ๐๐ถ๐ผ๐ป: Since the introduction of antiretroviral (ARV) drugs in 1996, the life expectancy of HIV-infected individuals has been nearly comparable to that of HIV-uninfected individuals. However, increasing evidence shows that antiretroviral therapy (ART) is associated with increased metabolic disorders, systemic inflammation, and hepatotoxicity. Tenofovir induces oxidative stress via mitochondrial DNA polymerase inhibition in HepG2 cells at chronic exposure. Although in vitro and in vivo studies have been performed to determine the effect of tenofovir on the inflammatory response, the inflammatory effect of this antiretroviral drug in liver cells still needs elucidation.
๐๐ถ๐บ: This study aimed to investigate tenofovir's potential pro- and anti-inflammatory properties in HepGโ human liver cells at different time frames.
๐ ๐ฒ๐๐ต๐ผ๐ฑ๐ผ๐น๐ผ๐ด๐: HepGโ cells were treated with tenofovir (1.2 ฮผM) over 24h and 120h; pro- and anti-inflammatory cytokines levels were assessed using a SimpleStep human ELISA kit specific to each analyte (IL-6, IL-1ฮฒ, TNF-ฮฑ, IL-10). Protein expression of p-NF-ฤธBp65, NF-ฤธBp65, p-IฤธBฮฑ, and IฤธBฮฑ was determined with Western blotting. A quantitative polymerase chain reaction assessed the mRNA expression of ๐๐-ฮบ๐๐ฑ65 and ๐๐ฌ๐ฮฑ.
๐ฅ๐ฒ๐๐๐น๐๐: Tenofovir significantly increased IL-6 and 10 levels, ๐๐-ฮบ๐๐ฑ65 mRNA expression and NF-ฮบBp65, p-NF-ฮบBp65 and p-IฮบBฮฑ protein expression. Additionally, a significant decrease in IL-1ฮฒ levels and ๐ฮบ๐ฮฑ mRNA expression at 24h were observed. After 120h, tenofovir-treated cells showed increased p-NF-ฮบBp65 and IฮบBฮฑ protein expression. Furthermore, a significant decrease in IL-6 and IL-10 levels, ๐๐-ฮบ๐๐ฑ65 and IฮบBฮฑ mRNA expression and NF-ฮบBp65 and p-IฮบBฮฑ protein expression were observed.
๐๐ผ๐ป๐ฐ๐น๐๐๐ถ๐ผ๐ป: The study demonstrated that tenofovir elevated the anti-inflammatory cytokines at acute exposure. Tenofovir increased pro-inflammatory cytokines and downregulated anti-inflammatory cytokines at chronic exposure of tenofovir in HepGโ human liver cells. The knowledge obtained from tenofovir-induced inflammatory changes can provide valuable information regarding tenofovirโs clinical use.
Description
Dissertation (MMed.Sc. ((Physiology))--University of the Free State, 2023
Keywords
Tenofovir, HepGโ cell line, ART, HIV/AIDS, inflammatory properties