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Tenofovir disoproxil fumarate mediates neuronal injury by inducing neurotoxicity

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European Journal of Clinical Microbiology & Infectious Diseases Aims and scope Submit manuscript

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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Data availability

All data can be provided by the corresponding author upon request.

Code availability

Not applicable.

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Funding

This work was supported by two fundings of Key Program of the Higher Education of Henan Province in China (NO. 212102310821 and NO. 222102310426) for Hongliang Liu and Juanmei Zhang, respectively, also provided partial supports for this work.

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Author notes

  1. Xiaotian Yang and Juanmei Zhang contributed equally to this work.

Authors and Affiliations

  1. Laboratory of Cancer Biomarkers and Liquid Biopsy, School of Pharmacy, Henan University, Kaifeng, 475004, Henan, China

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

  2. Ministry of Education Key Laboratory for Animal Pathogens and Biosafety, Zhengzhou, 450001, Henan, China

    Juanmei Zhang, Hongliang Liu & Dengke Bao

  3. Shenzhen Beike Bio-Technology Co., Ltd, Shenzhen, 518000, Guangdong, China

    Yanhong Cheng

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  1. Xiaotian Yang
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Xiaotian Yang, Juanmei Zhang, Dengke Bao and Hongliang Liu. The first draft of the manuscript was written by Xiaotian Yang and Juanmei Zhang, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Hongliang Liu or Dengke Bao.

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All experiments in this study were performed in accordance with relevant guidelines and regulations and were approved by Ethics Committee of Henan University.

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Yang, X., Zhang, J., Cheng, Y. et al. Tenofovir disoproxil fumarate mediates neuronal injury by inducing neurotoxicity. Eur J Clin Microbiol Infect Dis 42, 1195–1205 (2023). https://doi.org/10.1007/s10096-023-04654-1

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