Tiloke, C.Van Zyl, SanetVazi, Songezo2024-03-182024-03-182023http://hdl.handle.net/11660/12473Dissertation (MMed.Sc. ((Physiology))--University of the Free State, 2023𝗜𝗻𝘁𝗿𝗼𝗱𝘂𝗰𝘁𝗶𝗼𝗻: 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. 𝗔𝗶𝗺: This study aimed to investigate tenofovir's potential pro- and anti-inflammatory properties in HepG₂ human liver cells at different time frames. 𝗠𝗲𝘁𝗵𝗼𝗱𝗼𝗹𝗼𝗴𝘆: HepG₂ cells were treated with tenofovir (1.2 μM) 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-1β, TNF-α, IL-10). Protein expression of p-NF-ĸBp65, NF-ĸBp65, p-IĸBα, and IĸBα was determined with Western blotting. A quantitative polymerase chain reaction assessed the mRNA expression of 𝘕𝘍-κ𝘉𝘱65 and 𝘐𝘬𝘉α. 𝗥𝗲𝘀𝘂𝗹𝘁𝘀: Tenofovir significantly increased IL-6 and 10 levels, 𝘕𝘍-κ𝘉𝘱65 mRNA expression and NF-κBp65, p-NF-κBp65 and p-IκBα protein expression. Additionally, a significant decrease in IL-1β levels and 𝘐κ𝘉α mRNA expression at 24h were observed. After 120h, tenofovir-treated cells showed increased p-NF-κBp65 and IκBα protein expression. Furthermore, a significant decrease in IL-6 and IL-10 levels, 𝘕𝘍-κ𝘉𝘱65 and IκBα mRNA expression and NF-κBp65 and p-IκBα protein expression were observed. 𝗖𝗼𝗻𝗰𝗹𝘂𝘀𝗶𝗼𝗻: 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 HepG₂ human liver cells. The knowledge obtained from tenofovir-induced inflammatory changes can provide valuable information regarding tenofovir’s clinical use.enTenofovirHepG₂ cell lineARTHIV/AIDSinflammatory propertiesDissertationUniversity of the Free State