title: Influence of cyclosporine A on glomerular growth and the effect of mizoribine and losartan on cyclosporine nephrotoxicity in young rats.
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.
authors.affiliation: Department of Pediatrics, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.|Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Ji Hong
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Yeon Hee
authors.initials: YH
authors.lastname: Lee
authors.affiliation: Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Beom Jin
authors.initials: BJ
authors.lastname: Lim
authors.affiliation: Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Hyeon Joo
authors.initials: HJ
authors.lastname: Jeong
authors.affiliation: Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Pyung Kil
authors.initials: PK
authors.lastname: Kim
authors.affiliation: Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea.|Department of Pediatric Nephrology, Severance Children's Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Jae Il
authors.initials: JI
authors.lastname: Shin
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism*; D016572:Cyclosporine / Q000633:toxicity*; D006651:Histocytochemistry; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000517:prevention & control*; D007678:Kidney Glomerulus / Q000187:drug effects*; D019808:Losartan / Q000378:metabolism*; D008297:Male; D017207:Rats, Sprague-Dawley; D012263:Ribonucleosides / Q000378:metabolism*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D012263:Ribonucleosides; C010052:mizoribine; D016572:Cyclosporine; D019808:Losartan