Dimethyl Sulfoxide (DMSO) Exacerbates Cisplatin-induced Sensory Hair Cell Death in Zebrafish (Danio rerio)
Inner ear sensory hair cells die following exposure to aminoglycoside antibiotics or chemotherapeutics like cisplatin, leading to permanent auditory and/or balance deficits in humans. Zebrafish (Danio rerio) are used to study drug-induced sensory hair cell death since their hair cells are similar in...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Public Library of Science
2013
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| Online Access: | http://hdl.handle.net/1721.1/78920 |
| _version_ | 1826210529564164096 |
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| author | Gomez-Uribe, Phillip M. Mueller, Melissa A. Gleichman, Julia S. Kramer, Matthew D. Wang, Qi Sibrian-Vazquez, Martha Strongin, Robert M. Steyger, Peter S. Cotanche, Douglas Allen Matsui, Jonathan I. |
| author2 | Harvard University--MIT Division of Health Sciences and Technology |
| author_facet | Harvard University--MIT Division of Health Sciences and Technology Gomez-Uribe, Phillip M. Mueller, Melissa A. Gleichman, Julia S. Kramer, Matthew D. Wang, Qi Sibrian-Vazquez, Martha Strongin, Robert M. Steyger, Peter S. Cotanche, Douglas Allen Matsui, Jonathan I. |
| author_sort | Gomez-Uribe, Phillip M. |
| collection | MIT |
| description | Inner ear sensory hair cells die following exposure to aminoglycoside antibiotics or chemotherapeutics like cisplatin, leading to permanent auditory and/or balance deficits in humans. Zebrafish (Danio rerio) are used to study drug-induced sensory hair cell death since their hair cells are similar in structure and function to those found in humans. We developed a cisplatin dose-response curve using a transgenic line of zebrafish that expresses membrane-targeted green fluorescent protein under the control of the Brn3c promoter/enhancer. Recently, several small molecule screens have been conducted using zebrafish to identify potential pharmacological agents that could be used to protect sensory hair cells in the presence of ototoxic drugs. Dimethyl sulfoxide (DMSO) is typically used as a solvent for many pharmacological agents in sensory hair cell cytotoxicity assays. Serendipitously, we found that DMSO potentiated the effects of cisplatin and killed more sensory hair cells than treatment with cisplatin alone. Yet, DMSO alone did not kill hair cells. We did not observe the synergistic effects of DMSO with the ototoxic aminoglycoside antibiotic neomycin. Cisplatin treatment with other commonly used organic solvents (i.e. ethanol, methanol, and polyethylene glycol 400) also did not result in increased cell death compared to cisplatin treatment alone. Thus, caution should be exercised when interpreting data generated from small molecule screens since many compounds are dissolved in DMSO. |
| first_indexed | 2024-09-23T14:51:05Z |
| format | Article |
| id | mit-1721.1/78920 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T14:51:05Z |
| publishDate | 2013 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | mit-1721.1/789202022-09-29T10:58:05Z Dimethyl Sulfoxide (DMSO) Exacerbates Cisplatin-induced Sensory Hair Cell Death in Zebrafish (Danio rerio) Gomez-Uribe, Phillip M. Mueller, Melissa A. Gleichman, Julia S. Kramer, Matthew D. Wang, Qi Sibrian-Vazquez, Martha Strongin, Robert M. Steyger, Peter S. Cotanche, Douglas Allen Matsui, Jonathan I. Harvard University--MIT Division of Health Sciences and Technology Cotanche, Douglas Allen Inner ear sensory hair cells die following exposure to aminoglycoside antibiotics or chemotherapeutics like cisplatin, leading to permanent auditory and/or balance deficits in humans. Zebrafish (Danio rerio) are used to study drug-induced sensory hair cell death since their hair cells are similar in structure and function to those found in humans. We developed a cisplatin dose-response curve using a transgenic line of zebrafish that expresses membrane-targeted green fluorescent protein under the control of the Brn3c promoter/enhancer. Recently, several small molecule screens have been conducted using zebrafish to identify potential pharmacological agents that could be used to protect sensory hair cells in the presence of ototoxic drugs. Dimethyl sulfoxide (DMSO) is typically used as a solvent for many pharmacological agents in sensory hair cell cytotoxicity assays. Serendipitously, we found that DMSO potentiated the effects of cisplatin and killed more sensory hair cells than treatment with cisplatin alone. Yet, DMSO alone did not kill hair cells. We did not observe the synergistic effects of DMSO with the ototoxic aminoglycoside antibiotic neomycin. Cisplatin treatment with other commonly used organic solvents (i.e. ethanol, methanol, and polyethylene glycol 400) also did not result in increased cell death compared to cisplatin treatment alone. Thus, caution should be exercised when interpreting data generated from small molecule screens since many compounds are dissolved in DMSO. National Institutes of Health (U.S.) (DC010998) National Institutes of Health (U.S.) (NIH DC010231) Harvard College (1780- ) Sarah Fuller Foundation for Little Deaf Children 2013-05-17T16:55:35Z 2013-05-17T16:55:35Z 2013-02 2012-08 Article http://purl.org/eprint/type/JournalArticle 1932-6203 http://hdl.handle.net/1721.1/78920 Uribe PM, Mueller MA, Gleichman JS, Kramer MD, Wang Q, et al. (2013) Dimethyl Sulfoxide (DMSO) Exacerbates Cisplatin-induced Sensory Hair Cell Death in Zebrafish (Danio rerio). PLoS ONE 8(2). e55359. en_US http://dx.doi.org/10.1371/journal.pone.0055359 PLoS One Creative Commons Attribution http://creativecommons.org/licenses/by/2.5/ application/pdf Public Library of Science PLoS |
| spellingShingle | Gomez-Uribe, Phillip M. Mueller, Melissa A. Gleichman, Julia S. Kramer, Matthew D. Wang, Qi Sibrian-Vazquez, Martha Strongin, Robert M. Steyger, Peter S. Cotanche, Douglas Allen Matsui, Jonathan I. Dimethyl Sulfoxide (DMSO) Exacerbates Cisplatin-induced Sensory Hair Cell Death in Zebrafish (Danio rerio) |
| title | Dimethyl Sulfoxide (DMSO) Exacerbates Cisplatin-induced Sensory Hair Cell Death in Zebrafish (Danio rerio) |
| title_full | Dimethyl Sulfoxide (DMSO) Exacerbates Cisplatin-induced Sensory Hair Cell Death in Zebrafish (Danio rerio) |
| title_fullStr | Dimethyl Sulfoxide (DMSO) Exacerbates Cisplatin-induced Sensory Hair Cell Death in Zebrafish (Danio rerio) |
| title_full_unstemmed | Dimethyl Sulfoxide (DMSO) Exacerbates Cisplatin-induced Sensory Hair Cell Death in Zebrafish (Danio rerio) |
| title_short | Dimethyl Sulfoxide (DMSO) Exacerbates Cisplatin-induced Sensory Hair Cell Death in Zebrafish (Danio rerio) |
| title_sort | dimethyl sulfoxide dmso exacerbates cisplatin induced sensory hair cell death in zebrafish danio rerio |
| url | http://hdl.handle.net/1721.1/78920 |
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