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Molecules. 2018 Feb 7;23(2). pii: E346. doi: 10.3390/molecules23020346.

Suramin-Induced Neurotoxicity: Preclinical Models and Neuroprotective Strategies.

Author information

1
Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Klinik und Hochschulambulanz für Neurologie, Chariteplatz 1, 10117 Berlin, Germany. david.von-der-ahe@charite.de.
2
Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Klinik und Hochschulambulanz für Neurologie, Chariteplatz 1, 10117 Berlin, Germany. petra.huehnchen@charite.de.
3
Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Cluster of Excellence NeuroCure, 10117 Berlin, Germany. petra.huehnchen@charite.de.
4
Berlin Institute of Health, Anna-Louisa-Karsch 2, 10178 Berlin, Germany. petra.huehnchen@charite.de.
5
Burke-Cornell Medical Research Institute, White Plains, NY 10605, USA. mgbalkaya@yahoo.com.
6
Field Neurosciences Institute Laboratory for Restorative Neurology, Central Michigan University, Mt. Pleasant, MI 48859, USA. stperuzzaro@gmail.com.
7
Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Klinik und Hochschulambulanz für Neurologie, Chariteplatz 1, 10117 Berlin, Germany. Matthias.endres@charite.de.
8
Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Cluster of Excellence NeuroCure, 10117 Berlin, Germany. Matthias.endres@charite.de.
9
Berlin Institute of Health, Anna-Louisa-Karsch 2, 10178 Berlin, Germany. Matthias.endres@charite.de.
10
Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Center for Stroke Resarch Berlin, 10117 Berlin, Germany. Matthias.endres@charite.de.
11
German Center for Neurodegenerative Diseases (DZNE), 10117 Berlin, Germany. Matthias.endres@charite.de.
12
German Center for Cardiovascular Research (DZHK), Partner Site Berlin, 10117 Berlin, Germany. Matthias.endres@charite.de.
13
Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Klinik und Hochschulambulanz für Neurologie, Chariteplatz 1, 10117 Berlin, Germany. wolfgang.boehmerle@charite.de.
14
Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Cluster of Excellence NeuroCure, 10117 Berlin, Germany. wolfgang.boehmerle@charite.de.
15
Berlin Institute of Health, Anna-Louisa-Karsch 2, 10178 Berlin, Germany. wolfgang.boehmerle@charite.de.

Abstract

Suramin is a trypan blue analogon originally developed to treat protozoan infections, which was found to have diverse antitumor effects. One of the most severe side effects in clinical trials was the development of a peripheral sensory-motor polyneuropathy. In this study, we aimed to investigate suramin-induced neuropathy with a focus on calcium (Ca2+) homeostasis as a potential pathomechanism. Adult C57Bl/6 mice treated with a single injection of 250 mg/kg bodyweight suramin developed locomotor and sensory deficits, which were confirmed by electrophysiological measurements showing a predominantly sensory axonal-demyelinating polyneuropathy. In a next step, we used cultured dorsal root ganglia neurons (DRGN) as an in vitro cell model to further investigate underlying pathomechanisms. Cell viability of DRGN was significantly decreased after 24-hour suramin treatment with a calculated IC50 of 283 µM. We detected a suramin-induced Ca2+ influx into DRGN from the extracellular space, which could be reduced with the voltage-gated calcium channel (VGCC) inhibitor nimodipine. Co-incubation of suramin and nimodipine partially improved cell viability of DRGN after suramin exposure. In summary, we describe suramin-induced neurotoxic effects on DRGN as well as potentially neuroprotective agents targeting intracellular Ca2+ dyshomeostasis.

KEYWORDS:

TRP channels; calcium; neuroprotection; suramin; voltage-gated calcium channels

PMID:
29414872
PMCID:
PMC6017835
DOI:
10.3390/molecules23020346
[Indexed for MEDLINE]
Free PMC Article

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