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European Journal of Clinical Microbiology & Infectious Diseases

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22-08-2023 | Tenofovir | Original Article

Tenofovir disoproxil fumarate mediates neuronal injury by inducing neurotoxicity

Authors: Xiaotian Yang, Juanmei Zhang, Yanhong Cheng, Mengmeng Cui, Zhixiong Jiang, Chunhui Fan, Jiaxing Chen, Lixia Qi, Hongliang Liu, Dengke Bao

Published in: European Journal of Clinical Microbiology & Infectious Diseases | Issue 10/2023

Abstract

Purpose

Highly active antiretroviral therapy (HAART) is an accepted treatment option for patients with virus infection. Mounting evidence indicated that persistent HAART treatment is implicated with increased morbidity of HIV-associated neurocognitive disorders (HAND) in patients. Tenofovir disoproxil fumarate (TDF), a novel nucleotide reverse transcriptase inhibitor (NRTI), was used in patients with HIV co-infected with HBV. And it is still a vital first-line antiretroviral compounds in HAART. However, whether persistent treatment with TDF is involved in HAND development remains to be further elucidated. In this study, we aimed to discuss the neurotoxicity of TDF.

Methods

We used SH-SY5Y cells and primary neuronal cells to evaluate the neurotoxicity of TDF in vitro. The cytotoxicity of TDF on SH-SY5Y cells and primary neuronal cells was evaluated by the cell viability and LDH levels by MTT assay and LDH kit, respectively. Hoechst 33342 staining, TUNEL assay and flow cytometry were performed to evaluate the cells apoptosis. The intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) production were measured by commercial kits. In addition, the activation level of caspase-3 was evaluated using spectrophotometry and western blotting.

Results

Our results showed that TDF treatment significantly induced cell viability and induced apoptosis of SH-SY5Y cells and primary neuronal cells. Furthermore, the ROS levels and MDA productions were significantly up-regulated in nerve cells treated with TDF.

Conclusion

Our findings indicated that TDF may induce neuronal cell apoptosis through increasing the intracellular ROS and the expression level of caspase-3, which may be related to the increasing prevalence of HAND.

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Title: Tenofovir disoproxil fumarate mediates neuronal injury by inducing neurotoxicity
Authors: Xiaotian Yang
Juanmei Zhang
Yanhong Cheng
Mengmeng Cui
Zhixiong Jiang
Chunhui Fan
Jiaxing Chen
Lixia Qi
Hongliang Liu
Dengke Bao
Publication date: 22-08-2023
Publisher: Springer Berlin Heidelberg
Keywords: Tenofovir
Human Immunodeficiency Virus
Published in: European Journal of Clinical Microbiology & Infectious Diseases / Issue 10/2023
Print ISSN: 0934-9723
Electronic ISSN: 1435-4373
DOI: https://doi.org/10.1007/s10096-023-04654-1

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