Exposure to DMSO during infancy alters neurochemistry, social interactions, and brain morphology in long‐evans rats

Abstract

Introduction Dimethyl 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). Methods DMSO 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). Results 164 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.) 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. The chronic neurological effects of DMSO exposure reported here raise concerns about its neurotoxicity and consequent safety in human medical applications and clinical trials.

Modulation of the endoplasmic reticulum stress and unfolded protein response mitigates the behavioral effects of early-life stress

“…DMSO is routinely used in biological research as a solvent and a cryopreservative in bone marrow and organ transplants. However, data have accumulated showing that DMSO may produce both adverse and beneficial effects on brain tissue [ 71 – 75 ]. A small dose of 0.2 µl/g given for 5 days to juvenile rats has been shown to lead to global changes in the brain metabolome and increase oxidative stress and proteolysis markers.…”

“…A small dose of 0.2 µl/g given for 5 days to juvenile rats has been shown to lead to global changes in the brain metabolome and increase oxidative stress and proteolysis markers. However, only higher doses of DMSO (2 and 4 µl/g) have been shown to affect rat behavior, i.e., decreased social habits [ 75 ]. Another group demonstrated that DMSO (0.3–10 µl/g) produced widespread apoptosis in the developing brain [ 73 ].…”

p73α1, an Isoform of the p73 Tumor Suppressor, Modulates Lipid Metabolism and Cancer Cell Growth via Stearoyl-CoA Desaturase-1

“…Mobile phase gradient and mass spectrometry parameters were identical, as described previously [ 42 ]. Metabolomics was performed by GC-MS as previously described [ 43 ] and by high-resolution LC-MS/MS as described previously [ 44 ].…”

Combined Application of Dimethyl Sulfoxide and Ethanol Nasal Spray during COVID-19 Pandemic May Protect Healthcare Workers: A Randomized Controlled Trial

“…Severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) is a positive-sense single-stranded RNA virus that causes Coronavirus disease 2019 (COVID- 19). The coronavirus has affected a large population worldwide since the beginning of the pandemic in December 2019 in Wuhan, China.…”

“…SARS-CoV-2 spike protein plays a crucial role in binding to the angiotensin receptor and entering the lung cell, which disrupts this process, and the virus's particles cannot continue their life cycle (16,17). Studies show that ethanol and DMSO have the least toxicity in human cells and rats (18,19). Therefore, the use of a solution containing 3% DMSO and 20% ethanol as an intranasal inhalation spray may destroy the virus's structure, break the virus transmission chain, and reduce the pathogenicity of the virus.…”