Open AccessEffect of the oral iron chelator deferiprone in diabetic nephropathy rats
Author(s) -
Zou Chunbo,
Liu Xiaogang,
Liu Ruichan,
Wang Mingao,
Sui Manshu,
Mu Suhong,
Li Li,
Ji Liqi,
Xie Rujuan
Publication year - 2017
Publication title -
journal of diabetes
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.949
H-Index - 43
eISSN - 1753-0407
pISSN - 1753-0393
DOI - 10.1111/1753-0407.12420
Subject(s) - deferiprone , medicine , nitrotyrosine , nephropathy , pharmacology , immunohistochemistry , streptozotocin , diabetic nephropathy , inflammation , deferoxamine , diabetes mellitus , endocrinology , kidney , nitric oxide synthase , nitric oxide
Background The aim of the present study was to investigate the effects of the iron chelator deferiprone in diabetic nephropathy (DN) rats and the mechanisms involved. Methods Thirty‐two male Wistar rats (180–220 g, 6 weeks old) were randomly divided into a control group, a DN group and two DN groups treated with either 50 or 100 mg/kg per day deferiprone. The DN group was established by feeding of a high‐carbohydrate–fat diet and injection of 35 mg/kg streptozotocin into the vena caudalis. The duration of deferiprone treatment was 20 weeks. Histopathological changes were detected by hematoxylin–eosin and Masson staining, as well as transmission electron microscopy. Levels of nuclear factor (NF)‐κB, monocyte chemotactic protein (MCP)‐1, matrix metalloproteinase (MMP)‐9, tissue‐specific inhibitor of metalloproteinase (TIMP)‐1, cyclo‐oxygenase (COX)‐2, and nitrotyrosine were determined in kidney tissues using reverse transcription–polymerase chain reaction (RT‐PCR), western blotting, and immunohistochemistry. Results Histopathological observations showed that deferiprone treatment alleviated inflammation infiltrates and collagenous fibrosis in DN rats. Results from RT‐PCR and western blotting indicated that deferiprone inhibited the expression of NF‐κB, MCP‐1, COX‐2, and nitrotyrosine, which were overexpressed in DN rats. Immunohistochemistry showed that the mechanism of deferiprone action may involve regulation of MMP‐9 and TIMP‐1. Decreased MMP‐9 expression and increased TIMP‐1 expression in DN rats were significantly promoted and inhibited by deferiprone, respectively. Conclusion Iron chelation by oral deferiprone has a renoprotective effect in DN rats by relieving oxidative stress, inflammation, and fibrosis, which is related to the cytokines NF‐κB, MCP‐1, MMP‐9, TIMP‐1, COX‐2, and nitrotyrosine.