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

Abstract Bacterial 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 wit...

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Autores principales:	Haroon Mohammad, Nader S. Abutaleb, Alexandra M. Dieterly, L. Tiffany Lyle, Mohamed N. Seleem
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0d5e66fa42a74201b1071507c9212963
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spelling	oai:doaj.org-article:0d5e66fa42a74201b1071507c92129632021-12-02T14:42:01ZInvestigating auranofin for the treatment of infected diabetic pressure ulcers in mice and dermal toxicity in pigs10.1038/s41598-021-90360-x2045-2322https://doaj.org/article/0d5e66fa42a74201b1071507c92129632021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90360-xhttps://doaj.org/toc/2045-2322Abstract Bacterial 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.Haroon MohammadNader S. AbutalebAlexandra M. DieterlyL. Tiffany LyleMohamed N. SeleemNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Haroon Mohammad Nader S. Abutaleb Alexandra M. Dieterly L. Tiffany Lyle Mohamed N. Seleem Investigating auranofin for the treatment of infected diabetic pressure ulcers in mice and dermal toxicity in pigs
description	Abstract Bacterial 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.
format	article
author	Haroon Mohammad Nader S. Abutaleb Alexandra M. Dieterly L. Tiffany Lyle Mohamed N. Seleem
author_facet	Haroon Mohammad Nader S. Abutaleb Alexandra M. Dieterly L. Tiffany Lyle Mohamed N. Seleem
author_sort	Haroon Mohammad
title	Investigating auranofin for the treatment of infected diabetic pressure ulcers in mice and dermal toxicity in pigs
title_short	Investigating auranofin for the treatment of infected diabetic pressure ulcers in mice and dermal toxicity in pigs
title_full	Investigating auranofin for the treatment of infected diabetic pressure ulcers in mice and dermal toxicity in pigs
title_fullStr	Investigating auranofin for the treatment of infected diabetic pressure ulcers in mice and dermal toxicity in pigs
title_full_unstemmed	Investigating auranofin for the treatment of infected diabetic pressure ulcers in mice and dermal toxicity in pigs
title_sort	investigating auranofin for the treatment of infected diabetic pressure ulcers in mice and dermal toxicity in pigs
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/0d5e66fa42a74201b1071507c9212963
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Investigating auranofin for the treatment of infected diabetic pressure ulcers in mice and dermal toxicity in pigs

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