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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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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. |
format | Online Article Text |
id | pubmed-6017835 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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