title: 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.
authors.affiliation: Jiangsu Province Key Laboratory of Neurodegeneration, Department of Anatomy, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Chan
authors.initials: C
authors.lastname: Yuan
authors.affiliation: Jiangsu Province Key Laboratory of Neurodegeneration, Department of Anatomy, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Junying
authors.initials: J
authors.lastname: Gao
authors.affiliation: Jiangsu Province Key Laboratory of Neurodegeneration, Department of Anatomy, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Jichao
authors.initials: J
authors.lastname: Guo
authors.affiliation: Jiangsu Province Key Laboratory of Neurodegeneration, Department of Anatomy, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Bai
authors.affiliation: Department of Rehabilitation Sciences, University of Kentucky Center For Excellence in Rural Health, Hazard, Kentucky, United States of America.
authors.forename: Charles
authors.initials: C
authors.lastname: Marshall
authors.affiliation: Department of Neurology, the Affiliated Hospital of Anhui Medical University, Lu'an People's Hospital, Lu'an, Anhui, China.
authors.forename: Zhiyou
authors.initials: Z
authors.lastname: Cai
authors.affiliation: Jiangsu Province Key Laboratory of Neurodegeneration, Department of Anatomy, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Linmei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Jiangsu Province Key Laboratory of Neurodegeneration, Department of Anatomy, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Xiao
mesh_terms: D000818:Animals; D017209:Apoptosis; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D045304:Cytochromes c / Q000378:metabolism; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects*; D051379:Mice; D008928:Mitochondria; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D027342:Excitatory Amino Acid Transporter 2; D017382:Reactive Oxygen Species; D045304:Cytochromes c; D053148:Caspase 3; D004121:Dimethyl Sulfoxide