دورية أكاديمية
أعرض في EDS

Ebselen improves fungal keratitis through exerting anti-inflammation, anti-oxidative stress, and antifungal effects.

التفاصيل البيبلوغرافية
العنوان: Ebselen improves fungal keratitis through exerting anti-inflammation, anti-oxidative stress, and antifungal effects.
المؤلفون: Yu B; Department of Ophthalmology, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Qingdao, Shandong Province, 266003, China., Wang Q; Department of Ophthalmology, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Qingdao, Shandong Province, 266003, China., Zhang L; Department of Ophthalmology, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Qingdao, Shandong Province, 266003, China., Lin J; Department of Ophthalmology, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Qingdao, Shandong Province, 266003, China., Feng Z; Department of Ophthalmology, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Qingdao, Shandong Province, 266003, China., Wang Z; Department of Ophthalmology, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Qingdao, Shandong Province, 266003, China., Gu L; Department of Ophthalmology, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Qingdao, Shandong Province, 266003, China., Tian X; Department of Ophthalmology, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Qingdao, Shandong Province, 266003, China., Luan S; Department of Ophthalmology, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Qingdao, Shandong Province, 266003, China., Li C; Department of Ophthalmology, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Qingdao, Shandong Province, 266003, China. Electronic address: yankelicui@126.com., Zhao G; Department of Ophthalmology, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Qingdao, Shandong Province, 266003, China. Electronic address: zhaoguiqiu_good@126.com.
المصدر: Redox biology [Redox Biol] 2024 Jul; Vol. 73, pp. 103206. Date of Electronic Publication: 2024 May 23.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier, B.V Country of Publication: Netherlands NLM ID: 101605639 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2213-2317 (Electronic) Linking ISSN: 22132317 NLM ISO Abbreviation: Redox Biol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [Amsterdam]: Elsevier, B.V., [2013]-
مواضيع طبية MeSH: Organoselenium Compounds*/pharmacology , Organoselenium Compounds*/therapeutic use , Isoindoles* , Keratitis*/drug therapy , Keratitis*/microbiology , Oxidative Stress*/drug effects , Azoles*/pharmacology , Azoles*/therapeutic use , Antifungal Agents*/pharmacology , Antifungal Agents*/therapeutic use , Anti-Inflammatory Agents*/pharmacology , Anti-Inflammatory Agents*/therapeutic use, Animals ; Mice ; RAW 264.7 Cells ; Antioxidants/pharmacology ; Aspergillus fumigatus/drug effects ; Aspergillosis/drug therapy ; Aspergillosis/microbiology ; Eye Infections, Fungal/drug therapy ; Eye Infections, Fungal/microbiology ; Eye Infections, Fungal/metabolism ; Disease Models, Animal
مستخلص: Fungal keratitis is a severely vision-threatening corneal infection, where the prognosis depends on both fungal virulence and host immune defense. Inappropriate host responses can induce substantial inflammatory damage to the cornea. Therefore, in the treatment of fungal keratitis, it is important to concurrently regulate the immune response while efforts are made to eliminate the pathogen. Ebselen is a widely studied organo-selenium compound and has been demonstrated to have antifungal, antibacterial, anti-inflammatory, and oxidative stress-regulatory properties. The effectiveness of ebselen for the treatment of fungal keratitis remains unknown. In this study, ebselen was demonstrated to produce a marked inhibitory effect on Aspergillus fumigatus (A. fumigatus), including spore germination inhibition, mycelial growth reduction, and fungal biofilm disruption. The antifungal activity of ebselen was related to the cell membrane damage caused by thioredoxin (Trx) system inhibition-mediated oxidative stress. On the contrary, ebselen enhanced the antioxidation of Trx system in mammalian cells. Further, ebselen was proven to suppress the expressions of inflammatory mediators (IL-1β, IL-6, TNF-α, COX-2, iNOS, and CCL2) and reduce the production of oxidative stress-associated indicators (ROS, NO, and MDA) in fungi-stimulated RAW264.7 cells. In addition, ebselen regulated PI3K/Akt/Nrf2 and p38 MAPK signaling pathways, which contributed to the improvement of inflammation and oxidative stress. Finally, we verified the therapeutic effect of ebselen on mouse fungal keratitis. Ebselen improved the prognosis and reduced the fungal burden in mouse corneas. Expressions of inflammatory mediators, as well as the infiltration of macrophages and neutrophils in the cornea were also obviously decreased by ebselen. In summary, ebselen exerted therapeutic effects by reducing fungal load and protecting host tissues in fungal keratitis, making it a promising treatment for fungal infections.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
معلومات مُعتمدة: 81870632 , 82171029 , 81800800 National Natural Science Foundation of China; ( TSQN202103188 Taishan Scholars Program
فهرسة مساهمة: Keywords: Anti-oxidative; Ebselen; Fungal keratitis; Inflammation; Thioredoxin
المشرفين على المادة: 40X2P7DPGH (ebselen)
0 (Organoselenium Compounds)
0 (Isoindoles)
0 (Azoles)
0 (Antifungal Agents)
0 (Anti-Inflammatory Agents)
0 (Antioxidants)
تواريخ الأحداث: Date Created: 20240526 Date Completed: 20240612 Latest Revision: 20240919
رمز التحديث: 20240919
مُعرف محوري في PubMed: PMC11152752
DOI: 10.1016/j.redox.2024.103206
PMID: 38796864
قاعدة البيانات: MEDLINE
الوصف
تدمد:2213-2317
DOI:10.1016/j.redox.2024.103206