Dimethyl Sulfoxide (DMSO) Exacerbates Cisplatin-induced Sensory Hair Cell Death in Zebrafish (Danio rerio)
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{"title"=>"Dimethyl Sulfoxide (DMSO) Exacerbates Cisplatin-induced Sensory Hair Cell Death in Zebrafish (Danio rerio)", "type"=>"journal", "authors"=>[{"first_name"=>"Phillip M.", "last_name"=>"Uribe", "scopus_author_id"=>"55577734500"}, {"first_name"=>"Melissa A.", "last_name"=>"Mueller", "scopus_author_id"=>"55422178700"}, {"first_name"=>"Julia S.", "last_name"=>"Gleichman", "scopus_author_id"=>"55577795900"}, {"first_name"=>"Matthew D.", "last_name"=>"Kramer", "scopus_author_id"=>"55577584000"}, {"first_name"=>"Qi", "last_name"=>"Wang", "scopus_author_id"=>"55698104800"}, {"first_name"=>"Martha", "last_name"=>"Sibrian-Vazquez", "scopus_author_id"=>"8631898800"}, {"first_name"=>"Robert M.", "last_name"=>"Strongin", "scopus_author_id"=>"7006796589"}, {"first_name"=>"Peter S.", "last_name"=>"Steyger", "scopus_author_id"=>"6701464299"}, {"first_name"=>"Douglas A.", "last_name"=>"Cotanche", "scopus_author_id"=>"7004081928"}, {"first_name"=>"Jonathan I.", "last_name"=>"Matsui", "scopus_author_id"=>"7102676725"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"isbn"=>"1932-6203", "issn"=>"19326203", "pui"=>"368253986", "pmid"=>"23383324", "doi"=>"10.1371/journal.pone.0055359", "sgr"=>"84873251864", "scopus"=>"2-s2.0-84873251864"}, "id"=>"fd55416e-aa25-3173-b180-86c81ec139a4", "abstract"=>"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.", "link"=>"http://www.mendeley.com/research/dimethyl-sulfoxide-dmso-exacerbates-cisplatininduced-sensory-hair-cell-death-zebrafish-danio-rerio", "reader_count"=>29, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Researcher"=>5, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>8, "Student > Postgraduate"=>2, "Student > Master"=>6, "Professor"=>3, "Other"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Researcher"=>5, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>8, "Student > Postgraduate"=>2, "Student > Master"=>6, "Professor"=>3, "Other"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Biochemistry, Genetics and Molecular Biology"=>5, "Agricultural and Biological Sciences"=>11, "Medicine and Dentistry"=>4, "Neuroscience"=>2, "Chemistry"=>3, "Psychology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>4}, "Neuroscience"=>{"Neuroscience"=>2}, "Chemistry"=>{"Chemistry"=>3}, "Psychology"=>{"Psychology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>11}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>5}, "Unspecified"=>{"Unspecified"=>3}}, "reader_count_by_country"=>{"India"=>1}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/496866"], "description"=>"<p>Summary of LC/LR-ESI-MS analysis for DDP-TR-Cl<sub>2</sub> after incubation for 18 hours in methanol (MeOH) and dimethyl sulfoxide (DMSO).</p>", "links"=>[], "tags"=>["incubation", "18", "methanol", "dimethyl", "sulfoxide"], "article_id"=>167369, "categories"=>["Cancer", "Neuroscience", "Cell Biology", "Pharmacology"], "users"=>["Phillip M. Uribe", "Melissa A. Mueller", "Julia S. Gleichman", "Matthew D. Kramer", "Qi Wang", "Martha Sibrian-Vazquez", "Robert M. Strongin", "Peter S. Steyger", "Douglas A. Cotanche", "Jonathan I. Matsui"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0055359.t001", "stats"=>{"downloads"=>3, "page_views"=>19, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Summary_of_LC_LR_ESI_MS_analysis_for_DDP_TR_Cl_2_after_incubation_for_18_hours_in_methanol_MeOH_and_dimethyl_sulfoxide_DMSO_/167369", "title"=>"Summary of LC/LR-ESI-MS analysis for DDP-TR-Cl<sub>2</sub> after incubation for 18 hours in methanol (MeOH) and dimethyl sulfoxide (DMSO).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-19 16:05:39"}
  • {"files"=>["https://ndownloader.figshare.com/files/496273"], "description"=>"<p>Brn3c-GFP larvae were treated with either 0.5% DMSO, 1 mM cisplatin or 1 mM cisplatin plus a dose range of DMSO (0.001%–0.5%), fixed, and surviving hair cells in O2 neuromasts were imaged and counted. Increasing the concentration of DMSO reduced the number of O2 sensory hair cells. Larvae treated with 1 mM cisplatin and plus a DMSO dose greater than 0.01% had significantly fewer hair cells than larvae treated with 1 mM cisplatin alone. Results are the mean values ± SD. n = 18−31 neuromasts for each treatment group. **p<0.01 when individual treatments are compared to untreated controls.</p>", "links"=>[], "tags"=>["dmso", "cisplatin", "affects", "surviving", "cells"], "article_id"=>166778, "categories"=>["Cancer", "Neuroscience", "Cell Biology", "Pharmacology"], "users"=>["Phillip M. Uribe", "Melissa A. Mueller", "Julia S. Gleichman", "Matthew D. Kramer", "Qi Wang", "Martha Sibrian-Vazquez", "Robert M. Strongin", "Peter S. Steyger", "Douglas A. Cotanche", "Jonathan I. Matsui"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0055359.g004", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Varying_the_concentration_of_DMSO_with_a_constant_level_of_cisplatin_affects_the_number_of_surviving_hair_cells_present_in_the_neuromast_/166778", "title"=>"Varying the concentration of DMSO with a constant level of cisplatin affects the number of surviving hair cells present in the neuromast.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 16:02:36"}
  • {"files"=>["https://ndownloader.figshare.com/files/496076"], "description"=>"<p>Five-days post-fertilization Brn3c-GFP transgenic zebrafish were exposed to varying doses of cisplatin for four hours to determine at which dose approximately 50% of the hair cells die. The larvae were fixed, co-labeled with the nuclear dye TO-PRO-3 (blue), and the GFP-tagged hair cells (green) in the O2 neuromast were imaged using confocal microscopy. (A–B) <i>Z</i>-stack projections of two O2 neuromasts under different treatment conditions showing the entire neuromast structure. (C–D) Slices from the same neuromasts as in A, B demonstrating the membrane-bound GFP label surrounding the nuclear dye. (A, C) Hair cells appear normal in untreated controls. (B, D) Noticeably fewer hair cells are found in larvae treated with 1 mM cisplatin. (E) The mean number of hair cells per O2 neuromast (± SD) decreased as the dose of cisplatin increased when compared to untreated controls. n = 9−31 neuromasts for each treatment group. ***p<0.001 when individual treatments are compared to untreated controls.</p>", "links"=>[], "tags"=>["cisplatin"], "article_id"=>166589, "categories"=>["Cancer", "Neuroscience", "Cell Biology", "Pharmacology"], "users"=>["Phillip M. Uribe", "Melissa A. Mueller", "Julia S. Gleichman", "Matthew D. Kramer", "Qi Wang", "Martha Sibrian-Vazquez", "Robert M. Strongin", "Peter S. Steyger", "Douglas A. Cotanche", "Jonathan I. Matsui"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0055359.g002", "stats"=>{"downloads"=>1, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Dose_response_curve_following_cisplatin_treatment_/166589", "title"=>"Dose response curve following cisplatin treatment.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 16:01:37"}
  • {"files"=>["https://ndownloader.figshare.com/files/496359"], "description"=>"<p>Brn3c-GFP zebrafish were treated with 0.75% ethanol (EtOH), 0.75% methanol (MeOH), or 0.75% polyethylene glycol 400 (PEG 400) in the presence or absence of 1 mM cisplatin for four hours. The larvae were then fixed, mounted, and imaged. None of the solvents alone killed hair cells and were similar to control numbers. There was no statistical difference (NS) in the number of surviving hair cells when larvae were treated with 1 mM cisplatin with or without different organic solvents. There was, however, a statistically significant difference (p<0.05) between untreated or solvent-only-treated controls and cisplatin with or without organic solvents. Results are the mean values ± SD. n = 14−42 neuromasts for each treatment group.</p>", "links"=>[], "tags"=>["solvents", "exacerbate", "ototoxic"], "article_id"=>166868, "categories"=>["Cancer", "Neuroscience", "Cell Biology", "Pharmacology"], "users"=>["Phillip M. Uribe", "Melissa A. Mueller", "Julia S. Gleichman", "Matthew D. Kramer", "Qi Wang", "Martha Sibrian-Vazquez", "Robert M. Strongin", "Peter S. Steyger", "Douglas A. Cotanche", "Jonathan I. Matsui"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0055359.g005", "stats"=>{"downloads"=>2, "page_views"=>49, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Other_organic_solvents_do_not_exacerbate_the_ototoxic_effects_of_cisplatin_/166868", "title"=>"Other organic solvents do not exacerbate the ototoxic effects of cisplatin.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 16:03:04"}
  • {"files"=>["https://ndownloader.figshare.com/files/496549"], "description"=>"<p>HPLC traces for elution times of DDP-TR-Cl<sub>2</sub> incubated with (A) methanol or (B) DMSO for four hours at room temperature. Note the two new major peaks at 14.88 and 16.01 minutes in B. HPLC conditions: reversed phase Discovery C<sub>18</sub> column (250 × 2.1 mm, 5 mm); flow rate: 200 µL, sample volume: 5 µL, water:MeCN. Solvent gradient 95∶5 to 5∶95 in 30 minutes, wavelength detection; 580 nm.</p>", "links"=>[], "tags"=>["solvated", "dmso", "elution", "peaks", "compared", "ddp-tr"], "article_id"=>167055, "categories"=>["Cancer", "Neuroscience", "Cell Biology", "Pharmacology"], "users"=>["Phillip M. Uribe", "Melissa A. Mueller", "Julia S. Gleichman", "Matthew D. Kramer", "Qi Wang", "Martha Sibrian-Vazquez", "Robert M. Strongin", "Peter S. Steyger", "Douglas A. Cotanche", "Jonathan I. Matsui"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0055359.g007", "stats"=>{"downloads"=>1, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_DDP_TR_solvated_with_DMSO_has_additional_elution_peaks_compared_to_DDP_TR_solvated_in_methanol_/167055", "title"=>"DDP-TR solvated with DMSO has additional elution peaks compared to DDP-TR solvated in methanol.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 16:04:04"}
  • {"files"=>["https://ndownloader.figshare.com/files/496654"], "description"=>"<p>LR ESI-MS spectra of compounds eluting at (A) 14.88 min corresponding to DDP-TR-Cl-DMSO (i.e., with a DMSO adduct); (B) 16.1 minutes corresponding to DDP-TR-Cl-DMSO; (C) 19.5 minutes corresponding to DDP-TR-Cl<sub>2</sub>, and (D) 21.2 minutes corresponding to DDP-TR-Cl<sub>2</sub>. [M<sup>+</sup>] and [M+Na<sup>+</sup>] ions are observed. M<sup>+</sup>, molecular ion of target compound; M+Na<sup>+</sup>, molecular ion of target compound plus sodium.</p>", "links"=>[], "tags"=>["solvated", "dmso", "altered", "spectral", "peaks", "compared", "ddp-tr"], "article_id"=>167152, "categories"=>["Cancer", "Neuroscience", "Cell Biology", "Pharmacology"], "users"=>["Phillip M. Uribe", "Melissa A. Mueller", "Julia S. Gleichman", "Matthew D. Kramer", "Qi Wang", "Martha Sibrian-Vazquez", "Robert M. Strongin", "Peter S. Steyger", "Douglas A. Cotanche", "Jonathan I. Matsui"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0055359.g008", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_DDP_TR_solvated_with_DMSO_has_altered_spectral_peaks_compared_to_DDP_TR_solvated_in_methanol_/167152", "title"=>"DDP-TR solvated with DMSO has altered spectral peaks compared to DDP-TR solvated in methanol.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 16:04:37"}
  • {"files"=>["https://ndownloader.figshare.com/files/495963"], "description"=>"<p>(A) Lateral view of a 5 days post-fertilization transgenic zebrafish showing GFP expression in neuromasts that are found along the head and the body (bright dots) of the animal. (B) Higher magnification of the head region, with neuromasts containing brightly GFP-labeled hair cells (white arrows) and inner ear organs (white arrowheads) easily identifiable. The otic 2 (O2) and middle 1 (Mi1) neuromasts are highlighted as these are the two neuromasts from which data for this study were obtained. The zebrafish optic tectum (T) is another structure that is also labeled with GFP.</p>", "links"=>[], "tags"=>["neuromasts", "brn3c-gfp", "transgenic"], "article_id"=>166461, "categories"=>["Cancer", "Neuroscience", "Cell Biology", "Pharmacology"], "users"=>["Phillip M. Uribe", "Melissa A. Mueller", "Julia S. Gleichman", "Matthew D. Kramer", "Qi Wang", "Martha Sibrian-Vazquez", "Robert M. Strongin", "Peter S. Steyger", "Douglas A. Cotanche", "Jonathan I. Matsui"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0055359.g001", "stats"=>{"downloads"=>3, "page_views"=>84, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Location_of_neuromasts_on_Brn3c_GFP_transgenic_zebrafish_/166461", "title"=>"Location of neuromasts on Brn3c-GFP transgenic zebrafish.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 16:00:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/496182"], "description"=>"<p>Zebrafish were treated with embryo medium (control), 0.5% DMSO, two different concentrations of cisplatin (0.5 mM or 1 mM), or cisplatin (0.5 mM or 1 mM) with 0.5% DMSO. Representative images of (A) control neuromasts, (B) neuromasts exposed to 1 mM cisplatin, and (C) neuromasts exposed to 1 mM cisplatin and 0.5% DMSO. When compared to a control O2 neuromast (A), fewer hair cells were present in the O2 neuromast of a 1 mM cisplatin-treated larva (B). When cisplatin is co-incubated with 0.5% DMSO (C), even fewer hair cells remain within the neuromast. (D) When larvae were treated with 0.5% DMSO in conjunction with cisplatin, there was a significant reduction in the number of hair cells when compared to cisplatin treatment alone indicating a synergistic effect of DMSO and cisplatin. Results are the mean values ± SD. n = 13−51 neuromasts for each treatment group. ***p<0.001.</p>", "links"=>[], "tags"=>["dmso", "cisplatin", "compromises", "morphology", "kills"], "article_id"=>166693, "categories"=>["Cancer", "Neuroscience", "Cell Biology", "Pharmacology"], "users"=>["Phillip M. Uribe", "Melissa A. Mueller", "Julia S. Gleichman", "Matthew D. Kramer", "Qi Wang", "Martha Sibrian-Vazquez", "Robert M. Strongin", "Peter S. Steyger", "Douglas A. Cotanche", "Jonathan I. Matsui"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0055359.g003", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Co_treatment_with_DMSO_and_cisplatin_compromises_hair_cell_morphology_and_kills_hair_cells_/166693", "title"=>"Co-treatment with DMSO and cisplatin compromises hair cell morphology and kills hair cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 16:02:10"}
  • {"files"=>["https://ndownloader.figshare.com/files/496449"], "description"=>"<p>Brn3c-GFP zebrafish were treated with 2 µg/mL DDP-TR dissolved in either methanol or 0.1% DMSO for two to forty-eight minutes and then fixed and imaged. (A) Low levels of DDP-TR fluorescence (red) were found in the O2 hair cells of methanol-treated zebrafish after two minutes. (B) More DDP-TR fluorescence was present in the hair cells of 0.1% DMSO-treated animals after two minutes. (C) DMSO increased levels of DDP-TR fluorescence into neuromast hair cells over time compared to DDP-TR plus methanol-treated fish. Results are the mean values ± SD. n = 15−125 individual hair cells per time point per treatment. **p<0.01.</p>", "links"=>[], "tags"=>["texas", "fluorescence", "cells", "ddp-tr", "solubilized", "dmso"], "article_id"=>166949, "categories"=>["Cancer", "Neuroscience", "Cell Biology", "Pharmacology"], "users"=>["Phillip M. Uribe", "Melissa A. Mueller", "Julia S. Gleichman", "Matthew D. Kramer", "Qi Wang", "Martha Sibrian-Vazquez", "Robert M. Strongin", "Peter S. Steyger", "Douglas A. Cotanche", "Jonathan I. Matsui"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0055359.g006", "stats"=>{"downloads"=>1, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_More_Texas_Red_fluorescence_in_hair_cells_when_DDP_TR_is_solubilized_in_DMSO_than_in_methanol_/166949", "title"=>"More Texas Red fluorescence in hair cells when DDP-TR is solubilized in DMSO than in methanol.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 16:03:32"}
  • {"files"=>["https://ndownloader.figshare.com/files/496767"], "description"=>"<p>Five dpf zebrafish larvae were treated with embryo medium (white bar), 100 µM neomycin sulfate (black bar), 0.5% DMSO (striped bar), or both for 1 hour (cross-hatched bar), and then washed three times in embryo medium. The larvae were allowed to recover in embryo medium for three hours as described previously <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0055359#pone.0055359-Harris1\" target=\"_blank\">[25]</a>, and then fixed. Although the neomycin treatment resulted in significantly fewer sensory hair cells, co-treating the larvae with both DMSO and neomycin did not cause more hair cell death than neomycin alone. Results are the mean values ± SD. n = 10−12 neuromasts for each treatment group. *p<0.05 when individual treatments are compared to untreated controls.</p>", "links"=>[], "tags"=>["exacerbate", "neomycin-induced", "sensory"], "article_id"=>167279, "categories"=>["Cancer", "Neuroscience", "Cell Biology", "Pharmacology"], "users"=>["Phillip M. Uribe", "Melissa A. Mueller", "Julia S. Gleichman", "Matthew D. Kramer", "Qi Wang", "Martha Sibrian-Vazquez", "Robert M. Strongin", "Peter S. Steyger", "Douglas A. Cotanche", "Jonathan I. Matsui"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0055359.g009", "stats"=>{"downloads"=>1, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_DMSO_does_not_exacerbate_neomycin_induced_sensory_hair_cell_death_/167279", "title"=>"DMSO does not exacerbate neomycin-induced sensory hair cell death.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 16:05:12"}

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Relative Metric

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