title: Iron chelator alleviates tubulointerstitial fibrosis in diabetic nephropathy rats by inhibiting the expression of tenascinC and other correlation factors.
abstract: Tubulointerstitial fibrosis is the final common pathway to diabetic nephropathy. However, only a few drugs are responsible for this pathologic process. We investigated the possible effect of deferiprone (iron chelator) treatment on experimental diabetic nephropathy (DN) rats, as well as the mechanisms involved in this process. Diabetic nephropathy was induced in rats by feeding on high-carbohydrate-fat food and injecting streptozotocin. After 20 weeks of deferiprone treatment, tubulointerstitial morphology was detected by staining with hematoxylin-eosin and Masson's trichrome. Tubulointerstitial fibrosis was measured using the point-counting technique. Biochemical parameters including fasting glucose, insulin resistance (IR), serum iron, ferritin, transferrin saturation (TS), and urinary albumin/creatinine ratio (UA/C) were detected in diabetic nephropathy models. Semiquantitative RT-PCR, western blot, and immunohistochemistry were utilized for evaluating mRNA and protein levels of tenascin C, fibronectin 1 (Fn1), TGF-β1, and collagen IV in nephridial tissue, respectively. Malonialdehyde (MDA) and superoxide dismutase (SOD) were determined by pyrogallol and thiobarbituric acid method. Tubulointerstitial fibrosis was significantly ameliorated after deferiprone treatment, and both mRNA and protein expressions of profibrotic factors were inhibited in treatment groups. Meanwhile, high levels of serum iron, ferritin, TS, and UA/C were observed in DN rats. These factors were down-regulated by deferiprone treatment. Furthermore, deferiprone effectively relieved serum IR and regulated oxidative stress process. Our results demonstrated the anti-fibrosis potential and renoprotective effects of deferiprone for diabetic nephropathy, and this process was partially mediated by tenascin C blocking.
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Str, Nangang District, Harbin, People's Republic of China.
authors.forename: Chunbo
authors.initials: C
authors.lastname: Zou
authors.forename: Rujuan
authors.initials: R
authors.lastname: Xie
authors.forename: Yushi
authors.initials: Y
authors.lastname: Bao
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Liu
authors.forename: Manshu
authors.initials: M
authors.lastname: Sui
authors.forename: Suhong
authors.initials: S
authors.lastname: M
authors.forename: Shuang
authors.initials: S
authors.lastname: Li
authors.forename: Huiqing
authors.initials: H
authors.lastname: Yin
mesh_terms: D000818:Animals; D000077543:Deferiprone; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007502:Iron Chelating Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D011728:Pyridones / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D019063:Tenascin / Q000378:metabolism*
chemical_list: D007502:Iron Chelating Agents; D011728:Pyridones; D019063:Tenascin; D000077543:Deferiprone; D008315:Malondialdehyde; D013482:Superoxide Dismutase