کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8270331 | 1534969 | 2014 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Osthole improves an accelerated focal segmental glomerulosclerosis model in the early stage by activating the Nrf2 antioxidant pathway and subsequently inhibiting NF-κB-mediated COX-2 expression and apoptosis
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کلمات کلیدی
PGE2Col-IVCCRRLUCOX-2Nrf2GPXFSGSHO-1TLCROS - ROSOsthole - استوولImmunohistochemistry - ایمونوهیستوشیمیIHC - ایمونوهیستوشیمیBUN - خوبdihydroethidium - دی هیدروتیدیمCyclooxygenase-2 - سیکلوکوکسیژناز2nuclear factor E2-related factor 2 - عامل فاکتور هسته ای E2 عامل 2Nrf2 pathway - مسیر nrf2urea nitrogen - نیتروژن اورهheme oxygenase 1 - همای اکسیژناز 1DHE - وProstaglandin E2 - پروستاگلاندین E2creatinine - کراتینینthin-layer chromatography - کروماتوگرافی نازک لایهCollagen IV - کلاژن IVCreatinine clearance - کلیرانس کراتینینglutathione peroxidase - گلوتاتیون پراکسیدازFocal segmental glomerulosclerosis - گلومرول اسکلروز بخش مرکزی فوکوسReactive oxygen species - گونههای فعال اکسیژن
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Inflammatory reactions and oxidative stress are implicated in the pathogenesis of focal segmental glomerulosclerosis (FSGS), a common chronic kidney disease with relatively poor prognosis and unsatisfactory treatment regimens. Previously, we showed that osthole, a coumarin compound isolated from the seeds of Cnidium monnieri, can inhibit reactive oxygen species generation, NF-κB activation, and cyclooxygenase-2 expression in lipopolysaccharide-activated macrophages. In this study, we further evaluated its renoprotective effect in a mouse model of accelerated FSGS (acFSGS), featuring early development of proteinuria, followed by impaired renal function, glomerular epithelial cell hyperplasia lesions (a sensitive sign that precedes the development of glomerular sclerosis), periglomerular inflammation, and glomerular hyalinosis/sclerosis. The results show that osthole significantly prevented the development of the acFSGS model in the treated group of mice. The mechanisms involved in the renoprotective effects of osthole on the acFSGS model were mainly a result of an activated Nrf2-mediated antioxidant pathway in the early stage (proteinuria and ischemic collapse of the glomeruli) of acFSGS, followed by a decrease in: (1) NF-κB activation and COX-2 expression as well as PGE2 production, (2) podocyte injury, and (3) apoptosis. Our data support that targeting the Nrf2 antioxidant pathway may justify osthole being established as a candidate renoprotective compound for FSGS.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Free Radical Biology and Medicine - Volume 73, August 2014, Pages 260-269
Journal: Free Radical Biology and Medicine - Volume 73, August 2014, Pages 260-269
نویسندگان
Shun-Min Yang, Yi-Lin Chan, Kuo-Feng Hua, Jia-Ming Chang, Hui-Ling Chen, Yung-Jen Tsai, Yu-Juei Hsu, Louis Kuoping Chao, Yang Feng-Ling, Yu-Ling Tsai, Shih-Hsiung Wu, Yih-Fuh Wang, Change-Ling Tsai, Ann Chen, Shuk-Man Ka,