Treatment With Dimethyl Fumarate Attenuates Calcineurin Inhibitor-induced Nephrotoxicity
| Autor: | Kelly Vo, M. Takasu, Shiri Li, Clarence E. Foster, Seyed H. Farzaneh, Nosratola D. Vaziri, Chie Takasu, Christine Pham, Hirohito Ichii, Michael J. Stamos, Shuman Liu, Lourdes Robles |
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| Rok vydání: | 2015 |
| Předmět: |
Graft Rejection
Male medicine.medical_specialty Kidney Disease medicine.medical_treatment Dimethyl Fumarate Calcineurin Inhibitors NF-E2-Related Factor 1 Pharmacology medicine.disease_cause Kidney Nitric Oxide Medical and Health Sciences Organ transplantation Article Antioxidants Nephrotoxicity Nitric oxide Rats Sprague-Dawley chemistry.chemical_compound Fumarates Malondialdehyde Medicine Animals Peroxidase Transplantation Dimethyl fumarate business.industry Prevention Organ Transplantation Rats Calcineurin Immunosuppressive drug chemistry 5.1 Pharmaceuticals Creatinine Immunology Cyclosporine Surgery Sprague-Dawley Development of treatments and therapeutic interventions business Oxidative stress Immunosuppressive Agents |
| Zdroj: | Transplantation, vol 99, iss 6 Takasu, C; Vaziri, ND; Li, S; Robles, L; Vo, K; Takasu, M; et al.(2015). Treatment with dimethyl fumarate attenuates calcineurin inhibitor-induced nephrotoxicity. Transplantation, 99(6), 1144-1150. doi: 10.1097/TP.0000000000000647. UC Irvine: Retrieved from: http://www.escholarship.org/uc/item/28t8p9qf |
| DOI: | 10.1097/TP.0000000000000647. |
| Popis: | Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. Background. Cyclosporine A (CsA) is an immunosuppressive drug which has been widely used to prevent rejection after organ transplantation. However, its therapeutic use is limited by nephrotoxicity, in part mediated by oxidative stress. The present study aims to investigate the protective effects of dimethyl fumarate (DMF) on CsA-induced nephrotoxicity by enhancing the antioxidant defense system. Methods. Male Sprague-Dawley rats were treated with CsA (n = 8, 20 mg/kg per day intraperitoneally) or CsA + DMF (n = 7, 50 mg/kg per day orally) for 28 days. Renal function, histopathology, malondialdehyde (MDA), myeloperoxidase levels, and antioxidant enzyme expression were determined. Results. The DMF cotreatment ameliorated CsA-induced renal dysfunction as evidenced by significant decrease in serum creatinine (CsA 0.79 ± 0.02 mg/dL vs CsA + DMF 0.62 ± 0.04 mg/dL, P = 0.001) and urea (CsA 66.9 ± 0.4 mg/dL vs CsA + DMF 53.3 ± 2.6 mg/dl, P < 0.0001) levels, as well as improvement of creatinine clearance. Dimethyl fumarate also significantly decreased serum MDA and renal tissue MDA and myeloperoxidase contents. The protein expression of NAD(P)H quinone oxidoreductase-1, a major cellular antioxidant and detoxifying enzyme, was significantly enhanced by DMF administration in kidney. Conclusion.s Administration of DMF has a protective potential against CsA nephrotoxicity. The protection afforded by DMF is mediated in part through inhibiting oxidative stress and inflammation and enhancing the antioxidant capacity. |
| Databáze: | OpenAIRE |
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