کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6163240 | 1249422 | 2011 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Peroxisome proliferator-activated receptor-α is renoprotective in doxorubicin-induced glomerular injury
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کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
بیماریهای کلیوی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Peroxisome proliferator-activated receptor-α is renoprotective in doxorubicin-induced glomerular injury Peroxisome proliferator-activated receptor-α is renoprotective in doxorubicin-induced glomerular injury](/preview/png/6163240.png)
چکیده انگلیسی
Doxorubicin (DOX) is an anthracycline antibiotic utilized in antitumor therapy; however, its clinical use is frequently impeded by renal toxic effects. As peroxisome proliferator-activated receptor-α (PPAR-α) has renoprotective effects in drug-related kidney injuries, we tested its ability to inhibit DOX-induced renal injury. Although both male PPAR-α knockout mice and their wild-type littermates (pure 129/SvJ background) had significant proteinuria 4 weeks after DOX treatment, those with deletion of PPAR-α had more severe proteinuria. This was associated with more serious podocyte foot process effacement compared with wild-type mice. In contrast, the PPAR-α agonist fenofibrate effectively reduced proteinuria and attenuated DOX-induced podocyte foot process effacement. Consistently, glomerular nephrin expression was significantly lower in the knockout compared with wild-type mice following DOX treatment. Fenofibrate therapy significantly blunted the reduction in glomerular nephrin levels in DOX-treated wild-type mice. In cultured podocytes, DOX induced apoptosis, increased cleaved caspase-3 levels, and decreased Bcl-2 expression, all attenuated by pretreatment with fenofibrate. Thus, PPAR-α deficiency exacerbates DOX-related renal injury, in part, due to increased podocyte apoptosis.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Kidney International - Volume 79, Issue 12, 2 June 2011, Pages 1302-1311
Journal: Kidney International - Volume 79, Issue 12, 2 June 2011, Pages 1302-1311
نویسندگان
Yunfeng Zhou, Xiaomu Kong, Pan Zhao, Hang Yang, Lihong Chen, Jing Miao, Xiaoyan Zhang, Jichun Yang, Jie Ding, Youfei Guan,