Effect of the oral iron chelator deferiprone in diabetic nephropathy rats.
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.


CONCLUSIONS
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.
Department of Nephrology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Chunbo
C
Zou
Department of Nephrology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Xiaogang
X
Liu
Department of Nephrology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Ruichan
R
Liu
Department of Nephrology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Mingao
M
Wang
Department of Nephrology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Manshu
M
Sui
Department of Nephrology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Suhong
S
Mu
Department of Nephrology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Li
L
Li
Department of Nephrology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Liqi
L
Ji
Department of Nephrology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Rujuan
R
Xie
D000284:Administration, Oral; D000818:Animals; D015153:Blotting, Western; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D000077543:Deferiprone; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D003928:Diabetic Nephropathies / Q000209:etiology / Q000517:prevention & control*; D004040:Dietary Carbohydrates / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D007150:Immunohistochemistry; D007502:Iron Chelating Agents / Q000008:administration & dosage / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D020011:Protective Agents / Q000008:administration & dosage / Q000494:pharmacology; D011728:Pyridones / Q000008:administration & dosage / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D018932:Chemokine CCL2; D004040:Dietary Carbohydrates; D007502:Iron Chelating Agents; D016328:NF-kappa B; D020011:Protective Agents; D011728:Pyridones; D019715:Tissue Inhibitor of Metalloproteinase-1; D000077543:Deferiprone; C002744:3-nitrotyrosine; D014443:Tyrosine; D051546:Cyclooxygenase 2; D020780:Matrix Metalloproteinase 9
deferiprone; diabetic nephropathy; fibrosis; inflammation; oxidative stress; 去铁酮; 氧化应激; 炎症; 糖尿病肾病; 纤维化