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Evaluation of Cytotoxic, Necrotic, Apoptotic, and Autophagic Effects of Methamphetamine and 3,4-Methylenedioxymethamphetamine on U-87 MG (Glial) and B104-1–1 (Neuronal) Cell Lines

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Abstract

Methamphetamine (MA) and 3,4-methylenedioxymethamphetamine (MDMA) are empathogen (entactogen) psychoactive designer drugs which are mainly used for recreational purposes. Both MA and MDMA are central nervous system stimulants which are classified as monoamine neurotransmitter reuptake inhibitors. They have strong cytotoxic effects on dopaminergic and serotonergic neurons. Neurotoxicities of MA and MDMA by glial activation have been shown. The present work has investigated and measured cytotoxic, necrotic and apoptotic, and autophagic effects of MA and MDMA on U-87 MG (glial) and B104-1–1 (neuronal) cell lines by janus green, ethidium bromide/acridine orange, and monodansylcadaverine/propidium iodide staining to evaluate and compare their effects on glial and neuronal cells, respectively. The results of the present work showed that: (1) MDMA induced more potent mitochondrial toxicity, stronger necrotic and autophagic effects than MA in both B104-1–1 (neuronal) and U-87 MG (glial) cell lines; (2) although MDMA induced stronger apoptotic effect than MA on U-87 MG cell line, it had equal apoptotic effect on B104-1–1 cell line with MA; and (3) MDMA induced more potent mitochondrial toxicity, stronger necrotic, apoptotic, and autophagic effects than MA in B104-1–1 cell line than U-87 MG cell line.

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Funding

This work has been supported by Iran University of Medical Sciences & Health Services (Grant no. 14776, January 19, 2020).

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Authors and Affiliations

  1. Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran

    Asieh Hosseini & Seyed Vahid Shetab-Boushehri

  2. Department of Nutrition, Science and Research Branch, Islamic Azad University, Tehran, Iran

    Seyed Mohammad-Hossein Shetab-Boushehri

  3. Ameretat Shimi Pharmaceutical Co, Tehran, Iran

    Seyed Vahid Shetab-Boushehri

Authors
  1. Asieh Hosseini
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  2. Seyed Mohammad-Hossein Shetab-Boushehri
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  3. Seyed Vahid Shetab-Boushehri
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Contributions

1) Dr. Asieh Hosseini cultured the cell lines, wrote the Introduction and Materials & Methods of the manuscript, and plotted some graphs. 2) Mr. Seyed Mohammad-Hossein Shetab-Boushehri helped in preparation of solutions and reagents, measurement of protein concentration, photography from the cells, and plotting some graphs. 3) Dr. Seyed Vahid Shetab-Boushehri incubated the cell lines with methamphetamine and MDMA, measured cytotoxicity, necrosis, apoptosis, and autophagy, and wrote Results and Discussion of the Manuscript.

Corresponding author

Correspondence to Seyed Vahid Shetab-Boushehri.

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Ethics Approval

The study was ethically approved by Iran University of Medical Sciences ethics committee and performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments (Approval ID: IR.IUMS.REC.1398.1093).

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The authors declare no competing interests.

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Hosseini, A., Shetab-Boushehri, S.MH. & Shetab-Boushehri, S.V. Evaluation of Cytotoxic, Necrotic, Apoptotic, and Autophagic Effects of Methamphetamine and 3,4-Methylenedioxymethamphetamine on U-87 MG (Glial) and B104-1–1 (Neuronal) Cell Lines. Neurotox Res 40, 1499–1515 (2022). https://doi.org/10.1007/s12640-022-00543-1

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  • DOI: https://doi.org/10.1007/s12640-022-00543-1

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