Investigating auranofin for the treatment of infected diabetic pressure ulcers in mice and dermal toxicity in pigs

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dc.contributor.authorMohammad, Haroonen
dc.contributor.authorAbutaleb, Nader S.en
dc.contributor.authorDieterly, Alexandra M.en
dc.contributor.authorLyle, L. Tiffanyen
dc.contributor.authorSeleem, Mohamed N.en
dc.contributor.departmentBiomedical Sciences and Pathobiologyen
dc.date.accessioned2021-08-05T18:02:30Zen
dc.date.available2021-08-05T18:02:30Zen
dc.date.issued2021-05-25en
dc.date.updated2021-08-05T18:02:26Zen
dc.description.abstractBacterial infection of pressure ulcers (PUs) are a notable source of hospitalization for individuals with diabetes. This study evaluated the safety profile and efficacy of auranofin to treat diabetic PUs infected with methicillin-resistant Staphylococcus aureus (MRSA). PUs were infected with MRSA in diabetic TALLYHO/JngJ mice and then treated with topical auranofin (2%), topical mupirocin (2%), or oral clindamycin (30 mg/kg) for four days. PUs were harvested post-treatment to enumerate bacterial burden and determine expression of cytokines/growth factors. Landrace cross pigs were exposed topically to auranofin (1%, 2%, and 3%) for 4–14 days and evaluated for signs of localized or systemic toxicity. Auranofin eradicated MRSA in PUs within four days (7.92-log10 reduction) in contrast to mupirocin (2.15-log10 reduction) and clindamycin (0.73-log10 reduction). Additionally, auranofin treatment resulted in decreased expression of pro-inflammatory cytokines and increased expression of biomarkers associated with re-epithelization of wounded tissue, confirmed with histopathologic analysis. No significant histopathologic lesions were present on porcine skin sites exposed to topical auranofin. Additionally, minimal accumulation of plasma gold and no systemic toxicity was observed in pigs exposed to topical auranofin. Auranofin appears to be a potent and safe topical agent to further investigate for treatment of mild-to-moderate MRSA-infected diabetic PUs.en
dc.description.versionPublished versionen
dc.format.extent10 page(s)en
dc.format.mimetypeapplication/pdfen
dc.identifierARTN 10935 (Article number)en
dc.identifier.doihttps://doi.org/10.1038/s41598-021-90360-xen
dc.identifier.eissn2045-2322en
dc.identifier.issn2045-2322en
dc.identifier.issue1en
dc.identifier.orcidSeleem, Mohamed [0000-0003-0939-0458]en
dc.identifier.other10.1038/s41598-021-90360-x (PII)en
dc.identifier.pmid34035383 (pubmed)en
dc.identifier.urihttp://hdl.handle.net/10919/104585en
dc.identifier.volume11en
dc.language.isoenen
dc.publisherNature Researchen
dc.relation.urihttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000659136700023&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=930d57c9ac61a043676db62af60056c1en
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectANTIBACTERIAL ACTIVITYen
dc.subjectREPURPOSING AURANOFINen
dc.subjectSAFETYen
dc.subjectEFFICACYen
dc.subjectMOUSEen
dc.subjectDRUGen
dc.titleInvestigating auranofin for the treatment of infected diabetic pressure ulcers in mice and dermal toxicity in pigsen
dc.title.serialScientific Reportsen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherArticleen
dc.type.otherJournalen
dcterms.dateAccepted2021-04-28en
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/Veterinary Medicineen
pubs.organisational-group/Virginia Tech/Veterinary Medicine/Biomedical Sciences and Pathobiologyen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Veterinary Medicine/CVM T&R Facultyen

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