Despite the triumph of highly active antiretroviral therapy (HAART) in anti-HIV infection, more than half of the HIV infection individuals receiving antiretroviral therapy acquire HIV-associated neurocognitive disorder (HAND). Previously researches had reported that the HAART neurotoxicity is implicated in HAND-related morbidity. The molecular mechanism of HAND is not clear. Tenofovir disoproxil fumarate (TDF) is a novel nucleotide reverse transcriptase inhibitor (NRTI), which was recommended as first-line therapeutic schedule for free AIDS antiviral drugs. Whether the neurotoxicity of TDF is associated with HAND is not well known. In this study, the cell viability of TDF-treated pheochromocytoma cells (PC-12) line was detected using MTT assay, while apoptosis was evaluated by Hoechst 33342 staining, TUNEL assay, as well as flow cytometry. In addition, the level of reactive oxygen species and BAX protein expression were evaluated using DCFH-DA staining and western blotting. The results showed that the proliferation of PC-12 cells was significantly inhibited by TDF. The morphological assay, TUNEL assay and flow cytometry showed that TDF efficiently triggered apoptosis in PC-12 cells. The reactive oxygen species levels were BAX expression was markedly up-regulated in PC-12 cells after treatment with TDF. These findings indicated that TDF may induce PC-12 cell apoptosis. TDF has neural toxicity effect that is relevant to the cell apoptosis, which may be related to the increasing prevalence of HAND.
Keywords: Apoptosis; HIV-associated neurocognitive disorder; Neurotoxicity; Pheochromocytoma cells; Tenofovir disoproxil fumarate.
Copyright © 2018. Published by Elsevier B.V.