Ebselen oxide attenuates mechlorethamine dermatotoxicity in the mouse ear vesicant model.
Identifieur interne : 000043 ( Main/Exploration ); précédent : 000042; suivant : 000044Ebselen oxide attenuates mechlorethamine dermatotoxicity in the mouse ear vesicant model.
Auteurs : Hemanta C Rao Tumu [États-Unis] ; Benedette J. Cuffari [États-Unis] ; Maria A. Pino [États-Unis] ; Jerzy Palus [Pologne] ; Magdalena Pi Tka-Ottlik [Pologne] ; Blase Billack [États-Unis]Source :
- Drug and chemical toxicology [ 1525-6014 ] ; 2020.
Abstract
Mechlorethamine (HN2) is an alkylating agent and sulfur mustard mimetic. Topical exposure to HN2 is associated with tissue blistering. Previous work in our laboratory has shown that ebselen (EB-1) possesses anti-vesicant, anti-inflammatory, anti-bacterial, anti-fungal, and cytoprotective properties, both in vivo and in vitro. We recently reported that ebselen oxide (EB-2), an analog of EB-1 with a tetravalent selenium atom, also possesses anti-bacterial and anti-fungal activity and confers cytoprotection against HN2 in vitro. The purpose of the present study was to determine the vesicant countermeasure potential of EB-2 using the mouse ear vesicant model (MEVM). Compared to control ears, mouse ears exposed to a single dose of HN2 (0.500 µmol/ear) showed an increase in wet weights, ear thickness, hyperplasia, vesication, and inflammatory cell infiltration after 24 h. Fluorescence microscopy of terminal deoxynucleotidyl transferase (TdT) dUTP nick end labeling (TUNEL)-stained sections showed that the occurrence of apoptosis extended from the epidermis of the HN2-treated side, all the way to the contralateral epidermis. In contrast, HN2-exposed ears treated topically with EB-2 at a test dose of 0.250 mg/ear showed a significant decrease in wet weight (12% less vs. HN2 alone), morphometric thickness (13% less vs. HN2 alone), and vesication. In addition, TUNEL staining revealed that HN2 ears treated with EB-2 (0.250 mg/ear) showed a decrease in apoptosis as compared to the HN2 group. EB-2 also reduced the abundance of matrix metalloproteinase-9 (MMP-9) in ear tissues exposed to HN2. Taken together, our study demonstrates that EB-2 is an efficacious countermeasure to HN2.
DOI: 10.1080/01480545.2018.1488858
PubMed: 30257109
Affiliations:
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Cuffari</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Jamaica, NY, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Jamaica, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Pino, Maria A" sort="Pino, Maria A" uniqKey="Pino M" first="Maria A" last="Pino">Maria A. Pino</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Jamaica, NY, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Jamaica, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Department of Clinical Specialties, NYIT College of Osteopathic Medicine, Old Westbury, NY, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Clinical Specialties, NYIT College of Osteopathic Medicine, Old Westbury, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Palus, Jerzy" sort="Palus, Jerzy" uniqKey="Palus J" first="Jerzy" last="Palus">Jerzy Palus</name><affiliation wicri:level="1"><nlm:affiliation>Department of Organic Chemistry, Faculty of Chemistry, Wrocław University of Science and Technology, Wrocław, Poland.</nlm:affiliation><country xml:lang="fr">Pologne</country><wicri:regionArea>Department of Organic Chemistry, Faculty of Chemistry, Wrocław University of Science and Technology, Wrocław</wicri:regionArea><wicri:noRegion>Wrocław</wicri:noRegion></affiliation></author><author><name sortKey="Pi Tka Ottlik, Magdalena" sort="Pi Tka Ottlik, Magdalena" uniqKey="Pi Tka Ottlik M" first="Magdalena" last="Pi Tka-Ottlik">Magdalena Pi Tka-Ottlik</name><affiliation wicri:level="1"><nlm:affiliation>Department of Organic and Pharmaceutical Technology, Faculty of Chemistry, Wrocław University of Science and Technology, Wrocław, Poland.</nlm:affiliation><country xml:lang="fr">Pologne</country><wicri:regionArea>Department of Organic and Pharmaceutical Technology, Faculty of Chemistry, Wrocław University of Science and Technology, Wrocław</wicri:regionArea><wicri:noRegion>Wrocław</wicri:noRegion></affiliation></author><author><name sortKey="Billack, Blase" sort="Billack, Blase" uniqKey="Billack B" first="Blase" last="Billack">Blase Billack</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Jamaica, NY, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Jamaica, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author></analytic><series><title level="j">Drug and chemical toxicology</title><idno type="eISSN">1525-6014</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Mechlorethamine (HN2) is an alkylating agent and sulfur mustard mimetic. Topical exposure to HN2 is associated with tissue blistering. Previous work in our laboratory has shown that ebselen (EB-1) possesses anti-vesicant, anti-inflammatory, anti-bacterial, anti-fungal, and cytoprotective properties, both <i>in vivo</i> and <i>in vitro</i>. We recently reported that ebselen oxide (EB-2), an analog of EB-1 with a tetravalent selenium atom, also possesses anti-bacterial and anti-fungal activity and confers cytoprotection against HN2 <i>in vitro</i>. The purpose of the present study was to determine the vesicant countermeasure potential of EB-2 using the mouse ear vesicant model (MEVM). Compared to control ears, mouse ears exposed to a single dose of HN2 (0.500 µmol/ear) showed an increase in wet weights, ear thickness, hyperplasia, vesication, and inflammatory cell infiltration after 24 h. Fluorescence microscopy of terminal deoxynucleotidyl transferase (TdT) dUTP nick end labeling (TUNEL)-stained sections showed that the occurrence of apoptosis extended from the epidermis of the HN2-treated side, all the way to the contralateral epidermis. In contrast, HN2-exposed ears treated topically with EB-2 at a test dose of 0.250 mg/ear showed a significant decrease in wet weight (12% less vs. HN2 alone), morphometric thickness (13% less vs. HN2 alone), and vesication. In addition, TUNEL staining revealed that HN2 ears treated with EB-2 (0.250 mg/ear) showed a decrease in apoptosis as compared to the HN2 group. EB-2 also reduced the abundance of matrix metalloproteinase-9 (MMP-9) in ear tissues exposed to HN2. Taken together, our study demonstrates that EB-2 is an efficacious countermeasure to HN2.</div></front></TEI><pubmed><MedlineCitation Status="In-Process" Owner="NLM"><PMID Version="1">30257109</PMID><DateRevised><Year>2020</Year><Month>05</Month><Day>13</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1525-6014</ISSN><JournalIssue CitedMedium="Internet"><Volume>43</Volume><Issue>4</Issue><PubDate><Year>2020</Year><Month>Jul</Month></PubDate></JournalIssue><Title>Drug and chemical toxicology</Title><ISOAbbreviation>Drug Chem Toxicol</ISOAbbreviation></Journal><ArticleTitle>Ebselen oxide attenuates mechlorethamine dermatotoxicity in the mouse ear vesicant model.</ArticleTitle><Pagination><MedlinePgn>335-346</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1080/01480545.2018.1488858</ELocationID><Abstract><AbstractText>Mechlorethamine (HN2) is an alkylating agent and sulfur mustard mimetic. Topical exposure to HN2 is associated with tissue blistering. Previous work in our laboratory has shown that ebselen (EB-1) possesses anti-vesicant, anti-inflammatory, anti-bacterial, anti-fungal, and cytoprotective properties, both <i>in vivo</i> and <i>in vitro</i>. We recently reported that ebselen oxide (EB-2), an analog of EB-1 with a tetravalent selenium atom, also possesses anti-bacterial and anti-fungal activity and confers cytoprotection against HN2 <i>in vitro</i>. The purpose of the present study was to determine the vesicant countermeasure potential of EB-2 using the mouse ear vesicant model (MEVM). Compared to control ears, mouse ears exposed to a single dose of HN2 (0.500 µmol/ear) showed an increase in wet weights, ear thickness, hyperplasia, vesication, and inflammatory cell infiltration after 24 h. Fluorescence microscopy of terminal deoxynucleotidyl transferase (TdT) dUTP nick end labeling (TUNEL)-stained sections showed that the occurrence of apoptosis extended from the epidermis of the HN2-treated side, all the way to the contralateral epidermis. In contrast, HN2-exposed ears treated topically with EB-2 at a test dose of 0.250 mg/ear showed a significant decrease in wet weight (12% less vs. HN2 alone), morphometric thickness (13% less vs. HN2 alone), and vesication. In addition, TUNEL staining revealed that HN2 ears treated with EB-2 (0.250 mg/ear) showed a decrease in apoptosis as compared to the HN2 group. EB-2 also reduced the abundance of matrix metalloproteinase-9 (MMP-9) in ear tissues exposed to HN2. Taken together, our study demonstrates that EB-2 is an efficacious countermeasure to HN2.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Tumu</LastName><ForeName>Hemanta C Rao</ForeName><Initials>HCR</Initials><AffiliationInfo><Affiliation>Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Jamaica, NY, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cuffari</LastName><ForeName>Benedette J</ForeName><Initials>BJ</Initials><AffiliationInfo><Affiliation>Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Jamaica, NY, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pino</LastName><ForeName>Maria A</ForeName><Initials>MA</Initials><AffiliationInfo><Affiliation>Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Jamaica, NY, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Clinical Specialties, NYIT College of Osteopathic Medicine, Old Westbury, NY, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Palus</LastName><ForeName>Jerzy</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Organic Chemistry, Faculty of Chemistry, Wrocław University of Science and Technology, Wrocław, Poland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Piętka-Ottlik</LastName><ForeName>Magdalena</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Organic and Pharmaceutical Technology, Faculty of Chemistry, Wrocław University of Science and Technology, Wrocław, Poland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Billack</LastName><ForeName>Blase</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Jamaica, NY, USA.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2018</Year><Month>09</Month><Day>26</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Drug Chem Toxicol</MedlineTA><NlmUniqueID>7801723</NlmUniqueID><ISSNLinking>0148-0545</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">MMP-9</Keyword><Keyword MajorTopicYN="N">Mechlorethamine</Keyword><Keyword MajorTopicYN="N">dermatotoxicity </Keyword><Keyword MajorTopicYN="N">ebselen oxide</Keyword><Keyword MajorTopicYN="N">mouse ear vesicant model</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2018</Year><Month>9</Month><Day>27</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2018</Year><Month>9</Month><Day>27</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2018</Year><Month>9</Month><Day>27</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">30257109</ArticleId><ArticleId IdType="doi">10.1080/01480545.2018.1488858</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Pologne</li><li>États-Unis</li></country><region><li>État de New York</li></region></list><tree><country name="États-Unis"><region name="État de New York"><name sortKey="Tumu, Hemanta C Rao" sort="Tumu, Hemanta C Rao" uniqKey="Tumu H" first="Hemanta C Rao" last="Tumu">Hemanta C Rao Tumu</name></region><name sortKey="Billack, Blase" sort="Billack, Blase" uniqKey="Billack B" first="Blase" last="Billack">Blase Billack</name><name sortKey="Cuffari, Benedette J" sort="Cuffari, Benedette J" uniqKey="Cuffari B" first="Benedette J" last="Cuffari">Benedette J. Cuffari</name><name sortKey="Pino, Maria A" sort="Pino, Maria A" uniqKey="Pino M" first="Maria A" last="Pino">Maria A. Pino</name><name sortKey="Pino, Maria A" sort="Pino, Maria A" uniqKey="Pino M" first="Maria A" last="Pino">Maria A. Pino</name></country><country name="Pologne"><noRegion><name sortKey="Palus, Jerzy" sort="Palus, Jerzy" uniqKey="Palus J" first="Jerzy" last="Palus">Jerzy Palus</name></noRegion><name sortKey="Pi Tka Ottlik, Magdalena" sort="Pi Tka Ottlik, Magdalena" uniqKey="Pi Tka Ottlik M" first="Magdalena" last="Pi Tka-Ottlik">Magdalena Pi Tka-Ottlik</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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