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Published on: April 9, 2019
Beyond Viral Control: Tenofovir's Hidden Impact on Blood-Brain Barrier Endothelial Cells
Saarah Behardien1, Khayelihle Brian Makhathini1, Chontrelle Willemse1
1Neurobiology Research Group, Department of Medical Biosciences, Faculty of Natural Sciences, University of the Western Cape, Cape Town, South Africa.
Tenofovir treatments (TDF and TAF) impaired blood-brain barrier (BBB) function by disrupting endothelial cell division and increasing permeability, potentially impacting neurodegeneration in HIV patients.
Area of Science:
- Neuroscience
- Pharmacology
- Cell Biology
Background:
- The blood-brain barrier (BBB) protects the brain but is compromised by Human Immunodeficiency Virus (HIV).
- Antiretroviral (ARV) therapies, including Tenofovir, are crucial for HIV management.
- The cerebrovascular effects of Tenofovir-based ARVs are not fully understood.
Purpose of the Study:
- To investigate the impact of Tenofovir Disoproxil Fumarate (TDF) and Tenofovir Alafenamide (TAF) on the integrity of the blood-brain barrier (BBB).
- To assess the effects of TDF and TAF on murine brain endothelial cell function in vitro.
Main Methods:
- Murine brain endothelial cells (bEnd.5) were exposed to varying concentrations of TDF and TAF for 24-96 hours.
- Evaluated cell proliferation and cell cycle progression using flow cytometry.
- Assessed monolayer permeability by measuring Transendothelial Electrical Resistance (TEER).
Main Results:
- Both TDF and TAF treatments significantly inhibited endothelial cell proliferation by disrupting the S-phase of the cell cycle.
- Exposure to TDF and TAF led to increased BBB monolayer permeability.
- These effects were observed across the tested concentrations and durations.
Conclusions:
- Prolonged exposure to Tenofovir-based ARVs (TDF and TAF) compromises BBB integrity.
- Inhibition of endothelial cell division and altered barrier function may contribute to neurodegeneration in HIV patients on long-term therapy.
- Further research is warranted to elucidate the long-term neurological consequences of Tenofovir use in HIV treatment.
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