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

 Ji Hong Kim  ;  YeonHee Lee  ;  Beom Jin Lim  ;  Hyeon Joo Jeong  ;  Pyung Kil Kim  ;  Jae Il Shin 
 SCIENTIFIC REPORTS, Vol.6 : 22374, 2016 
Journal Title
Issue Date
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*
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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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
Kim, Ji Hong(김지홍) ORCID logo https://orcid.org/0000-0001-5352-5423
Shin, Jae Il(신재일) ORCID logo https://orcid.org/0000-0003-2326-1820
Lee, Yeon Hee(이연희)
Lim, Beom Jin(임범진) ORCID logo https://orcid.org/0000-0003-2856-0133
Jeong, Hyeon Joo(정현주) ORCID logo https://orcid.org/0000-0002-9695-1227
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