Dimethyl Sulfoxide Damages Mitochondrial Integrity and Membrane Potential in Cultured Astrocytes

Abstract

Dimethyl sulfoxide (DMSO) is a polar organic solvent that is used to dissolve neuroprotective or neurotoxic agents in neuroscience research. However, DMSO itself also has pharmacological and pathological effects on the nervous system. Astrocytes play a central role in maintaining brain homeostasis, but the effect and mechanism of DMSO on astrocytes has not been studied. The present study showed that exposure of astrocyte cultures to 1% DMSO for 24 h did not significantly affect cell survival, but decreased cell viability and glial glutamate transporter expression, and caused mitochondrial swelling, membrane potential impairment and reactive oxygen species production, and subsequent cytochrome c release and caspase-3 activation. DMSO at concentrations of 5% significantly inhibited cell variability and promoted apoptosis of astrocytes, accompanied with more severe mitochondrial damage. These results suggest that mitochondrial impairment is a primary event in DMSO-induced astrocyte toxicity. The potential cytotoxic effects on astrocytes need to be carefully considered during investigating neuroprotective or neurotoxic effects of hydrophobic agents dissolved by DMSO.

Effects of Ovariectomy and 17<i>β</i>-Estradiol Replacement on Dopamine D2 Receptors in Female Rats: Consequences on Sucrose, Alcohol, Water Intakes and Body Weight

“…Non-ovariectomized rats were treated for 10 days respectively with 17β-estradiol (5 µg/kg: [44]), bromocriptine mesylate (0.1 mg/kg: [45]), sulpiride (20 mg/kg: [46]) and a concomitant administration of "17β-estradiol + bromocriptine" or "17β-estradiol + sulpiride", and DMSO vehicle (0.7%: [47]). Precisely, thirty-six (36) nulliparous female rats, individually housed, were divided into 6 treatment groups (6 rats/treatment group) and were administered for 10 consecutive days as follows:…”

Implementation and Challenges of Direct Acoustic Dosing into Cell-Based Assays

“…3 The small-volume transfers enabled by ADE mitigate the impact of the use of DMSO on biological assays. DMSO is the routine solvent for pharmaceutical small-molecule compound collections; however, DMSO has been shown to induce a range of effects on cells, including differentiation, growth arrest, and reduced cell viability, [4][5][6] and DMSO tolerance in cell-based assays is typically 0.1% to 0.5% v/v. Miniaturization of assays into 384-well and 1536-well formats is also enabled.…”

Intrathecal Intermittent Orexin-A Causes Sympathetic Long-Term Facilitation and Sensitizes the Peripheral Chemoreceptor Response to Hypoxia in Rats

“…DMSO can adversely affect astrocyte function (Yuan et al, 2014), which may lead to unknown off-target effects. For this reason, many neuropharmacologic studies requiring DMSO to dissolve their neuroprotectant or neurotoxic drugs dilute the DMSO concentration.…”