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Suramin-Induced Neurotoxicity: Preclinical Models and Neuroprotective Strategies

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 sur...

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Autores principales: von der Ahe, David, Huehnchen, Petra, Balkaya, Mustafa, Peruzzaro, Sarah, Endres, Matthias, Boehmerle, Wolfgang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6017835/
https://www.ncbi.nlm.nih.gov/pubmed/29414872
http://dx.doi.org/10.3390/molecules23020346
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author von der Ahe, David
Huehnchen, Petra
Balkaya, Mustafa
Peruzzaro, Sarah
Endres, Matthias
Boehmerle, Wolfgang
author_facet von der Ahe, David
Huehnchen, Petra
Balkaya, Mustafa
Peruzzaro, Sarah
Endres, Matthias
Boehmerle, Wolfgang
author_sort von der Ahe, David
collection PubMed
description 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 (Ca(2+)) 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 IC(50) of 283 µM. We detected a suramin-induced Ca(2+) 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 Ca(2+) dyshomeostasis.
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spelling pubmed-60178352018-11-13 Suramin-Induced Neurotoxicity: Preclinical Models and Neuroprotective Strategies von der Ahe, David Huehnchen, Petra Balkaya, Mustafa Peruzzaro, Sarah Endres, Matthias Boehmerle, Wolfgang Molecules Article 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 (Ca(2+)) 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 IC(50) of 283 µM. We detected a suramin-induced Ca(2+) 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 Ca(2+) dyshomeostasis. MDPI 2018-02-07 /pmc/articles/PMC6017835/ /pubmed/29414872 http://dx.doi.org/10.3390/molecules23020346 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
von der Ahe, David
Huehnchen, Petra
Balkaya, Mustafa
Peruzzaro, Sarah
Endres, Matthias
Boehmerle, Wolfgang
Suramin-Induced Neurotoxicity: Preclinical Models and Neuroprotective Strategies
title Suramin-Induced Neurotoxicity: Preclinical Models and Neuroprotective Strategies
title_full Suramin-Induced Neurotoxicity: Preclinical Models and Neuroprotective Strategies
title_fullStr Suramin-Induced Neurotoxicity: Preclinical Models and Neuroprotective Strategies
title_full_unstemmed Suramin-Induced Neurotoxicity: Preclinical Models and Neuroprotective Strategies
title_short Suramin-Induced Neurotoxicity: Preclinical Models and Neuroprotective Strategies
title_sort suramin-induced neurotoxicity: preclinical models and neuroprotective strategies
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6017835/
https://www.ncbi.nlm.nih.gov/pubmed/29414872
http://dx.doi.org/10.3390/molecules23020346
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