HIV Protease Inhibitors Apoptotic Effect in SH-SY5Y Neuronal Cell Line

Paola Maura Tricarico, Rafael Freitas De Oliveira Franca, Sabrina Pacor, Valentina Ceglia, Sergio Crovella, Fulvio Celsi

Research output: Contribution to journalArticle

Abstract

Background: Prophylactic treatment regimens to prevent mother-to-child HIV transmission include protease inhibitors Lopinavir and Ritonavir. Lopinavir and Ritonavir have been reported to be able to induce intracellular oxidative stress in diverse cellular models, however scarce informations are available about protease inhibitor effects of in the central nervous system (CNS). In our study we evaluated the impact of protease inhibitors on a cell neuronal model. Methods: We treated a neuroblastoma cell line (SH-SY5Y) with increasing doses of Lopinavir and Ritonavir (0.1-1-10-25-50 μM), used alone or in combination, evaluating the impact of these drugs in terms of mitochondrial activity, with MTT cell proliferation assay; mRNA expression of heme oxygenase (HemeOH) and reactive oxygen species (ROS) levels with 2',7'-dichlorofluorescin diacetate (H2DCFDA) in order to assess oxidative stress; apoptotic cell death with flow cytometry. Results: We observed that Lopinavir and Ritonavir treatment, at 25 and/or 50 μM concentrations, induced mitochondrial damage, increase of heme oxygenase RNA expression levels and ROS generation, followed by apoptosis in SH-SY5Y. Conclusions: Our in vitro model demonstrates a damaging effect of HIV protease inhibitors on the neuroblastoma cell line, thus partially mimicking the impact of these drugs on the CNS of children born to HIV positive mothers undergone to antiretroviral treatment.

Original languageEnglish
Pages (from-to)1463-1470
Number of pages8
JournalCellular Physiology and Biochemistry
Volume39
Issue number4
DOIs
Publication statusPublished - Sep 1 2016

Keywords

  • Apoptosis
  • Lopinavir
  • Mitochondrial damage
  • Mother-to-child HIV transmission
  • Neuronal cell
  • Ritonavir

ASJC Scopus subject areas

  • Physiology

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  • Cite this

    Tricarico, P. M., De Oliveira Franca, R. F., Pacor, S., Ceglia, V., Crovella, S., & Celsi, F. (2016). HIV Protease Inhibitors Apoptotic Effect in SH-SY5Y Neuronal Cell Line. Cellular Physiology and Biochemistry, 39(4), 1463-1470. https://doi.org/10.1159/000447849