Inflammatory properties of tenofovir in human liver cells

Abstract

Background

Tenofovir is one of the antiretroviral (ARV) drugs used as a first-line regimen known to suppress HIV viral load successfully. However, its clinical application is limited by a lack of understanding of its inflammatory response in human liver cells. Liver toxicity has been linked to long-term use of tenofovir.

Objectives

This review was conducted to outline tenofovir's potential pro and anti-inflammatory properties in liver cells at acute and chronic exposure.

Methods

The relevant studies were analysed in PubMed, Google Scholar, Medline and Web of Science. This analysis outlined tenofovir's potential pro and anti-inflammatory properties in liver cells at acute and chronic exposure, with special attention to inflammatory markers.

Results

Tenofovir's acute and chronic usage is associated with mitochondrial toxicity, resulting in hepatocyte damage through mitochondrial DNA (mtDNA) depletion. Tenofovir has been shown to cause mitochondrial dysfunction and elevate mitochondrial reactive oxygen species (MtROS), resulting in hepatotoxicity. Enhanced generation of MtROS can activate the NF-κB signalling pathway through the IĸB kinase (IKK) complex system. NF-κB is an important pro-inflammatory transcription factor that plays a significant role in oxidative stress-induced inflammation. Following its activation, it can increase the transcription of various genes and subsequently regulate inflammation.

Conclusion

This review demonstrated that tenofovir exhibits its cytotoxic effect via induced mitochondrial dysfunction; however, its impact on liver inflammation is yet to be determined. Therefore, a study investigating tenofovir's inflammatory properties in HepG₂ cells at acute and chronic exposure is warranted.