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Influence of cyclosporine A on glomerular growth and the effect of mizoribine and losartan on cyclosporine nephrotoxicity in young rats

Authors
 Ji Hong Kim  ;  YeonHee Lee  ;  Beom Jin Lim  ;  Hyeon Joo Jeong  ;  Pyung Kil Kim  ;  Jae Il Shin 
Citation
 Scientific Reports, Vol.6 : 22374-22374, 2016 
Journal Title
 Scientific Reports 
ISSN
 2045-2322 
Issue Date
2016
MeSH
Animals ; Anti-Inflammatory Agents, Non-Steroidal/metabolism* ; Cyclosporine/toxicity* ; Histocytochemistry ; Kidney/pathology ; Kidney Diseases/chemically induced* ; Kidney Diseases/prevention & control* ; Kidney Glomerulus/drug effects* ; Losartan/metabolism* ; Male ; Rats, Sprague-Dawley ; Ribonucleosides/metabolism*
Abstract
The aim of this study was to evaluate the influence of cyclosporine A (CsA) on glomerular growth and the effect of mizoribine (MZR) and losartan (LSAR) on CsA-induced nephropathy in young rats. Six-week-old male Sprague-Dawley rats maintained on a low salt diet were given CsA (15 mg/kg), CsA and LSRT (30 mg/kg/day), CsA and MZR (5 mg/kg), or a combination of CsA, LSRT, and MZR for 4 and 7 weeks (two experiments) and compared with control group (olive oil-treated). Histopathology and glomerular size, inflammatory and fibrotic factors were studied. The score of acute CsA toxicity significantly decreased in the CsA + MZR group compared to the CsA group (p < 0.01). MZR and MZR + LSRT reduced tubulointerstitial fibrosis and TGF-β1 mRNA expression at 7 weeks. Osteopontin (OPN) mRNA expression was decreased at 7 weeks in MZR + LSRT (p < 0.01). Glomerular area decreased CsA group and recovered in MZR (p < 0.01) and MZR + LSRT (p < 0.01) at 7 weeks. This study demonstrated that MZR and LSRT had suppressive effects on inflammatory process in chronic CsA nephropathy and led to improvement of tubular damage, tubulointerstitial fibrosis and arteriolopathy by down regulation of OPN and TGF-β1 and glomerular size contraction.
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DOI
10.1038/srep22374
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pediatrics (소아청소년과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
김지홍(Kim, Ji Hong) ORCID logo https://orcid.org/0000-0001-5352-5423
신재일(Shin, Jae Il) ORCID logo https://orcid.org/0000-0003-2326-1820
이연희(Lee, Yeon Hee)
임범진(Lim, Beom Jin) ORCID logo https://orcid.org/0000-0003-2856-0133
정현주(Jeong, Hyeon Joo) ORCID logo https://orcid.org/0000-0002-9695-1227
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/146518
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