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- Title
GSPE Inhibits HMGB1 Release, Attenuating Renal IR-Induced Acute Renal Injury and Chronic Renal Fibrosis.
- Authors
Juan Zhan; Kun Wang; Conghui Zhang; Chunxiu Zhang; Yueqiang Li; Ying Zhang; Xiaoyan Chang; Qiaodan Zhou; Ying Yao; Yanyan Liu; Gang Xu
- Abstract
Grape seed proanthocyanindin extract (GSPE) is a polyphenolic bioflavonoid derived from grape seeds and has been widely studied for its potent antioxidant, anti-inflammatory and antitumor activities. HMGB1 is a newly discovered danger-associated molecular pattern (DAMP) that has potent proinflammatory effects once released by necrotic cells. However, the effect of GSPE on the HMGB1, and the relationship of those two with acute kidney injury and chronic kidney fibrosis are unknown. This study aimed to investigate the impact of GSPE on acute kidney injury and chronic fibrosis. C57bl/6 mice were subjected to bilateral ischemia/reperfusion (I/R) and unilateral I/R with or without GSPE administration. After bilateral I/R, mice administered GSPE had a marked improvement in renal function (BUN and Cr), decreased pathological damage and reduced inflammation. In unilateral I/R, mice subjected GSPE showed reduced tubulointerstitial fibrosis and decreased inflammatory reaction. The renoprotection of GSPE on both models was associated with the inhibition of HMGB1 nucleocytoplasmic shuttling and release, which can amplify the inflammation through binding to its downstream receptor TLR4 and facilitated P65 transcription. Thus, we have reason to believe that GSPE could be a good alternative therapy for the prevention and treatment of IR-induced renal injury and fibrosis in clinical practice.
- Subjects
BIOFLAVONOIDS; GRAPE seed extract; ANTIOXIDANTS; ANTINEOPLASTIC agents; FIBROSIS
- Publication
International Journal of Molecular Sciences, 2016, Vol 17, Issue 10, p1647
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms17101647