Next Article in Journal
Design, Synthesis, and Biological Evaluation of 2-(Benzylamino-2-Hydroxyalkyl)Isoindoline-1,3-Diones Derivatives as Potential Disease-Modifying Multifunctional Anti-Alzheimer Agents
Next Article in Special Issue
Therapeutic Potential of Oridonin and Its Analogs: From Anticancer and Antiinflammation to Neuroprotection
Previous Article in Journal
Weed Suppressing Potential and Isolation of Potent Plant Growth Inhibitors from Castanea crenata Sieb. et Zucc
Previous Article in Special Issue
Synthesis and Biological Evaluations of NO-Donating Oxa- and Aza-Pentacycloundecane Derivatives as Potential Neuroprotective Candidates
Article Menu
Issue 2 (February) cover image

Export Article

Open AccessArticle
Molecules 2018, 23(2), 346; https://doi.org/10.3390/molecules23020346

Suramin-Induced Neurotoxicity: Preclinical Models and Neuroprotective Strategies

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
2
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
3
Berlin Institute of Health, Anna-Louisa-Karsch 2, 10178 Berlin, Germany
4
Burke-Cornell Medical Research Institute, White Plains, NY 10605, USA
5
Field Neurosciences Institute Laboratory for Restorative Neurology, Central Michigan University, Mt. Pleasant, MI 48859, USA
6
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
7
German Center for Neurodegenerative Diseases (DZNE), 10117 Berlin, Germany
8
German Center for Cardiovascular Research (DZHK), Partner Site Berlin, 10117 Berlin, Germany
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 15 December 2017 / Revised: 23 January 2018 / Accepted: 3 February 2018 / Published: 7 February 2018
(This article belongs to the Special Issue Neuroprotective Agents)
Full-Text   |   PDF [1270 KB, uploaded 7 February 2018]   |  

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. View Full-Text
Keywords: suramin; calcium; neuroprotection; voltage-gated calcium channels; TRP channels suramin; calcium; neuroprotection; voltage-gated calcium channels; TRP channels
Figures

Figure 1a

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary material

SciFeed

Share & Cite This Article

MDPI and ACS Style

von der Ahe, D.; Huehnchen, P.; Balkaya, M.; Peruzzaro, S.; Endres, M.; Boehmerle, W. Suramin-Induced Neurotoxicity: Preclinical Models and Neuroprotective Strategies. Molecules 2018, 23, 346.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top