Adverse effects of methylene blue in peripheral neurons: An in vitro electrophysiology and cell culture study

Methylene blue (MB) is an effective treatment for methemoglobinemia, ifosfamide-induced encephalopathy, cyanide poisoning, and refractory vasoplegia. However, clinical case reports and preclinical studies indicate potentially neurotoxic activity of MB at certain concentrations. The exact mechanisms...

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Bibliographic Details
Published in:Molecular pain 2022-04, Vol.18, p.17448069221142523
Main Authors: Uhelski, Megan L, Johns, Malcolm E, Horrmann, Alec, Mohamed, Sadiq, Sohail, Ayesha, Khasabova, Iryna A, Simone, Donald A, Banik, Ratan K
Format: Article
Language:English
Subjects:
Action potential
Afterhyperpolarization
Animals
Axonogenesis
Case reports
Cell culture
Cell Culture Techniques
Cells, Cultured
Cyanides
Dorsal root ganglia
Electrical properties
Electrophysiology
Encephalopathy
Ganglia, Spinal - metabolism
Ifosfamide
Methemoglobinemia
Methylene blue
Methylene Blue - metabolism
Methylene Blue - pharmacology
Mice
Myenteric plexus
Neurotoxicity
Rats
Sensory neurons
Sensory Receptor Cells - metabolism
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Summary:Methylene blue (MB) is an effective treatment for methemoglobinemia, ifosfamide-induced encephalopathy, cyanide poisoning, and refractory vasoplegia. However, clinical case reports and preclinical studies indicate potentially neurotoxic activity of MB at certain concentrations. The exact mechanisms of MB neurotoxicity are not known, and while the effects of MB on neuronal tissue from different brain regions and myenteric ganglia have been examined, its effects on primary afferent neurons from dorsal root ganglia (DRG) have not been studied. Mouse DRG were exposed to MB (0.3–10 μM) in vitro to assess neurite outgrowth. Increasing concentrations of MB (0.3–10 μM) were associated with neurotoxicity as shown by a substantial loss of cells with neurite formation, particularly at 10 μM. In parallel experiments, cultured rat DRG neurons were treated with MB (100 μM) to examine how MB affects electrical membrane properties of small-diameter sensory neurons. MB decreased peak inward and outward current densities, decreased action potential amplitude, overshoot, afterhyperpolarization, increased action potential rise time, and decreased action potential firing in response to current stimulation. MB induced dose-dependent toxicity in peripheral neurons, in vitro. These findings are consistent with studies in brain and myenteric ganglion neurons showing increased neuronal loss and altered membrane electrical properties after MB application. Further research is needed to parse out the toxicity profile for MB to minimize damage to neuronal structures and reduce side effects in clinical settings.
ISSN:1744-8069
1744-8069
DOI:10.1177/17448069221142523