title: Protective effects of Mizoribine on Cyclosporine A nephropathy in rats.
abstract: The therapeutic benefits of Cyclosporine A (CsA) are often limited by the chronic nephrotoxicity of its long-term use. Chronic nephrotoxicity is manifested by renal function impairment and progressive histopathological kidney lesions characterized by tubular vacuolization, tubular necrosis, interstitial fibrosis, and afferent arteriolopathy. This study tested the hypothesis that the concurrent administration of Mizoribine (MZR) may improve chronic CsA nephrotoxicity. Sprague-Dawley male rats were divided into the following four groups: group 1, control (n = 6); group 2, treated with CsA alone (n = 5); group 3, treated with CsA and MZR (n = 4); and group 4, treated with MZR alone (n = 6). The anti-inflammatory and antifibrotic effects of MZR were studied by evaluating the concentrations of the inflammatory mediator, osteopontin, renal function, and histopathology. The interstitial fibrosis was stained blue with Elastica-Massontrichrome and the sections were quantified. The CsA-treated rats showed decreased renal function and increased histologic parameters in comparison with the control rats and also showed significantly increased interstitial fibrosis area and macrophage in comparison with the control rats. The CsA MZR treatment significantly improved the interstitial fibrosis area and macrophage in comparison with the CsA-treated rats. On the basis of these findings, we suggest MZR effectively attenuates renal macrophage accumulation and the progression of interstitial fibrosis.
authors: Department of Pediatrics, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan. satoshi-h@y6.dion.ne.jp
authors: Satoshi
authors: S
authors: Hara
authors: Daisuke
authors: D
authors: Umino
authors: Tomonosuke
authors: T
authors: Someya
authors: Shuichiro
authors: S
authors: Fujinaga
authors: Yoshiyuki
authors: Y
authors: Ohtomo
authors: Hitohiko
authors: H
authors: Murakami
authors: Toshiaki
authors: T
authors: Shimizu
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001835:Body Weight; D016572:Cyclosporine / Q000633:toxicity*; D018450:Disease Progression; D005355:Fibrosis; D007150:Immunohistochemistry / Q000379:methods; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007249:Inflammation; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D007674:Kidney Diseases / Q000188:drug therapy*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012263:Ribonucleosides / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D007166:Immunosuppressive Agents; D012263:Ribonucleosides; C010052:mizoribine; D016572:Cyclosporine