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

Investigating auranofin for the treatment of infected diabetic pressure ulcers in mice and dermal toxicity in pigs.
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研究了耳拟金用于治疗小鼠感染糖尿病压溃疡的治疗和猪皮肤毒性。

DOI:
10.1038/s41598-021-90360-x
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发表时间:
2021-05-25
期刊:
影响因子:
4.6
通讯作者:
Seleem MN
Seleem MN
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Mohammad H;Abutaleb NS;Dieterly AM;Lyle LT;Seleem MN

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压疮(PU)的细菌感染是糖尿病患者住院的一个重要原因。本研究评估了金诺芬治疗感染耐甲氧西林金黄色葡萄球菌 (MRSA) 的糖尿病 PU 的安全性和有效性。 PU 在糖尿病 TALLYHO/JngJ 小鼠中感染 MRSA,然后用局部金诺芬 (2%)、局部莫匹罗星 (2%) 或口服克林霉素 (30 mg/kg) 治疗四天。处理后收获PU以计算细菌负荷并确定细胞因子/生长因子的表达。长白杂交猪局部暴露于金诺芬(1%、2% 和 3%)4-14 天,并评估局部或全身毒性迹象。与莫匹罗星(减少 2.15-log10)和克林霉素(减少 0.73-log10)相比,金诺芬在四天内根除 PU 中的 MRSA(减少 7.92-log10)。此外,经组织病理学分析证实,金诺芬治疗导致促炎细胞因子的表达减少,以及与受伤组织的上皮再生相关的生物标志物的表达增加。暴露于局部金诺芬的猪皮肤部位没有出现明显的组织病理学损伤。此外,在暴露于局部金诺芬的猪中观察到血浆金的积累最小,并且没有全身毒性。金诺芬似乎是一种有效且安全的外用药物,可用于进一步研究治疗轻至中度 MRSA 感染的糖尿病 PU。
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.
DOI: 10.1177/1091581812462039
发表时间: 2012-11-01
影响因子: 2.2
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发表时间: 2020-04-29
期刊: SCIENTIFIC REPORTS
影响因子: 4.6
作者:
Mohammad, Haroon;Abutaleb, Nader S.;Seleem, Mohamed N.
通讯作者: Seleem, Mohamed N.