Abstract
IntroductionDimethyl sulfoxide (DMSO) is a widely used solvent to dissolve hydrophobic substances for clinical uses and experimental in vivo purposes. While usually regarded safe, our prior studies suggest changes to behavior following DMSO exposure. We therefore evaluated the effects of a five‐day, short‐term exposure to DMSO on postnatal infant rats (P6‐10).MethodsDMSO was intraperitoneally injected for five days at 0.2, 2.0, and 4.0 ml/kg body mass. One cohort of animals was sacrificed 24 hr after DMSO exposure to analyze the neurometabolic changes in four brain regions (cortex, hippocampus, basal ganglia, and cerebellum) by hydrophilic interaction liquid chromatography. A second cohort of animals was used to analyze chronic alterations to behavior and pathological changes to glia and neuronal cells later in life (P21‐P40).Results164 metabolites, including key regulatory molecules (retinoic acid, orotic acid, adrenic acid, and hypotaurine), were found significantly altered by DMSO exposure in at least one of the brain regions at P11 (p < .05). Behavioral tests showed significant hypoactive behavior and decreased social habits to the 2.0 and 4.0 ml DMSO/kg groups (p < .01). Significant increases in number of microglia and astrocytes at P40 were observed in the 4.0 ml DMSO/kg group (at p < .015.)ConclusionsDespite short‐term exposure at low, putatively nontoxic concentrations, DMSO led to changes in behavior and social preferences, chronic alterations in glial cells, and changes in essential regulatory brain metabolites. The chronic neurological effects of DMSO exposure reported here raise concerns about its neurotoxicity and consequent safety in human medical applications and clinical trials.
Highlights
Dimethyl sulfoxide (DMSO) is a widely used solvent to dissolve hydrophobic substances for clinical uses and experimental in vivo purposes
We evaluated the effects of a five-day, short-term exposure of DMSO during the critical phase of myelination in neonatal Long-Evans (LE)
We found that the 0.2 ml DMSO/kg group had nearly the same levels of DMSO incorporated as the sham-treated animals
Summary
Dimethyl sulfoxide (DMSO) is a widely used solvent to dissolve hydrophobic substances for clinical uses and experimental in vivo purposes. Significant increases in number of microglia and astrocytes at P40 were observed in the 4.0 ml DMSO/kg group (at p < .015.) Conclusions: Despite short-term exposure at low, putatively nontoxic concentrations, DMSO led to changes in behavior and social preferences, chronic alterations in glial cells, and changes in essential regulatory brain metabolites. Dimethyl sulfoxide (DMSO) is regarded as a safe solvent, commonly used in in vivo experiments. It is widely available as an over- the-counter, topical pain-relieving agent, and can be purchased in large quantities with no regulation. DMSO is fully miscible with other aqueous substances and can form chemical associations with many different molecules and matrixes, including metal ions, drugs, and components of tissue, blood, plasma, and spinal fluid (Wong & Reinertson, 1984)
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