Synergistic protective effects of mizoribine and angiotensin II receptor blockade on cyclosporine A nephropathy in rats
| Autor: | Toshiaki Shimizu, Hitohiko Murakami, Mayu Nakagawa, Tomonosuke Someya, Yoshiyuki Ohtomo, Satoshi Hara, Amane Endo, Koji Sakuraya, Yayoi Murano, Shuichiro Fujinaga |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Angiotensin receptor Pharmacology Body weight Polymerase Chain Reaction Drug synergism Rats sprague dawley Nephropathy Rats Sprague-Dawley Angiotensin Receptor Antagonists polycyclic compounds Animals Medicine Mizoribine business.industry Body Weight Drug Synergism medicine.disease Rats Blockade Pediatrics Perinatology and Child Health Cyclosporine Kidney Diseases Ribonucleosides business Immunosuppressive Agents medicine.drug |
| Zdroj: | Pediatric Research. 75:38-44 |
| ISSN: | 1530-0447 0031-3998 |
| DOI: | 10.1038/pr.2013.169 |
| Popis: | Chronic cyclosporine A (CsA) nephrotoxicity is manifested by renal dysfunction, progressive histopathological kidney lesions characterized by afferent arteriolopathy, and tubulointerstitial fibrosis. In addition to the direct toxic effect of CsA, many other etiological factors such as angiotensin II, transforming growth factor (TGF)-β, and macrophage infiltration are involved in this pathogenesis. This study investigated the hypothesis that concomitant administration of mizoribine (MZR) and angiotensin II receptor blockade (ARB) may prevent CsA nephrotoxicity in rats.Sprague-Dawley male rats were divided into the following seven groups: group 1, treated with CsA; group 2, treated with CsA + MZR; group 3, treated with CsA + valsartan (Val); group 4, treated with CsA + MZR + Val; group 5, treated with MZR; group 6, treated with Val; and group 7, controls (n = 5 each). Renal histopathology and the effect of CsA-induced nephrotoxicity on inflammatory mediators were evaluated.Results of this study demonstrated that ARB administration significantly decreased arteriolopathy and that in comparison with monotherapy, concomitant administration of MZR and ARB further decreased arteriolopathy, fibrosis, macrophage infiltration, and TGF-β1 mRNA expression associated with CsA nephrotoxicity.These findings indicate that MZR and ARB combination treatment provides synergistic protective effects against chronic CsA nephrotoxicity. |
| Databáze: | OpenAIRE |
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