title: Protective effects of eplerenone on podocyte injury in adriamycin nephropathy rats.
abstract: To investigate the protective effects of eplerenone on adriamycin-induced renal injury and the possible mechanisms involved, 36 male Sprague-Dawley rats were randomly divided into control group, adriamycin nephropathy (AN) group and eplerenone-treated group (100 mg·kg(-1)·d(-1) eplerenone). Blood pressure, 24-h urinary protein, serum potassium, sodium and creatinine were measured 28 days after adriamycin injection (a single tail intravenous injection of 6.5 mg/kg adriamycin). The morphological changes of renal tissues were observed by light and electron microscopy. Immunohistochemistry and Western blotting were performed to examine the expression of TGF-β(1) and desmin in renal cortex. The results showed that 28 days after adriamycin injection, there were no significant changes in the level of serum potassium, sodium, creatinine concentrations and blood pressure values in the rats of the three groups. Meanwhile, the 24-h proteinuria excretion in the AN group was significantly higher than that in the control group (P<0.01), but that in the eplerenone-treated group was substantially reduced when compared with that in the AN group (P<0.05). Mild mesangial cell proliferation and matrix expansion, diffuse deformation and confluence of foot processes in podocytes were found in the AN group. By contrast, rats in the eplerenone-treated group exhibited obvious attenuation of these morphological lesions. The protein expression of TGF-β(1) and desmin in the AN group was markedly up-regulated in contrast to that in the control group (P<0.01), whereas that in the eplerenone-treated group was much lower than in the AN group (P<0.05). It was concluded that eplerenone may ameliorate the proteinuria and the development of pathological alteration in adriamycin-induced nephropathy presumably via the inhibition of cytokine release, and restore the morphology of podocytes independent of its blood pressure-lowing effects.
authors.affiliation: Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.|Department of Nephrology, Yantai Mountain Hospital, Yantai, 264000, China.
authors.forename: Zhan
authors.initials: Z
authors.lastname: Fang
authors.affiliation: Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: He
authors.affiliation: Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Xifeng
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Jianshe
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Neurobiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. xfmeng@mails.tjmu.edu.cn.
authors.forename: Xianfang
authors.initials: X
authors.lastname: Meng
mesh_terms: D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D015536:Down-Regulation / Q000187:drug effects; D004317:Doxorubicin; D000077545:Eplerenone; D007674:Kidney Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D007678:Kidney Glomerulus / Q000378:metabolism; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D050199:Podocytes / Q000187:drug effects / Q000473:pathology*; D020011:Protective Agents / Q000627:therapeutic use; D011507:Proteinuria / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D016207:Cytokines; D000451:Mineralocorticoid Receptor Antagonists; D020011:Protective Agents; D013148:Spironolactone; D000077545:Eplerenone; D004317:Doxorubicin