title: Protective Effect of Edaravone Against Cyclosporine-Induced Chronic Nephropathy Through Antioxidant and Nitric Oxide Modulating Pathways in Rats.
abstract: BACKGROUND
  Cyclosporine A (CsA) is an immunosuppressant with therapeutic indications in various immunological diseases; however, its use is associated with chronic nephropathy. Oxidative stress has a crucial role in CsA-induced nephrotoxicity. The present study evaluates the protective effect of edaravone on CsA-induced chronic nephropathy and investigates its antioxidant and nitric oxide modulating property.
  
  
  METHODS
  Male Sprague-Dawley rats (n=66) were distributed into nine groups, including a control (group 1) (n=7). Eight groups received CsA (15 mg/kg) for 28 days while being treated. The groups were categorized as: Group 2: Vehicle (n=10)Groups 3, 4, and 5: Edaravone (1, 5, and 10 mg/kg) (n=7 each)Group 6: Diphenyliodonium chloride, a specific endothelial nitric oxide synthase (eNOS) inhibitor (n=7)Group 7: Aminoguanidine, a specific inducible nitric oxide synthase (iNOS) inhibitor (n=7)Group 8: Edaravone (10 mg/kg) plus diphenyliodonium chloride (n=7)Group 9: Edaravone (10 mg/kg) plus aminoguanidine (n=7) Blood urea nitrogen and serum creatinine levels, malondialdehyde, superoxide dismutase, and glutathione reductase enzyme activities were measured using standard kits. Renal histopathological evaluations and measurements of eNOS and iNOS gene expressions by RT-PCR were also performed. Data were analyzed using one-way analysis of variance (ANOVA) followed by Tukey's test (SPSS software version 18.0).
  
  
  RESULTS
  Edaravone (10 mg/kg) significantly attenuated CsA-induced oxidative stress, renal dysfunction, and kidney tissue injury. Aminoguanidine improved the renoprotective effect of edaravone. Edaravone reduced the elevated mRNA level of iNOS, but could not alter the level of eNOS mRNA significantly.
  
  
  CONCLUSIONS
  Edaravone protects against CsA-induced chronic nephropathy using antioxidant property and probably through inhibiting iNOS gene expression.
authors.affiliation: Department of Pharmacology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Elahe
authors.initials: E
authors.lastname: Sattarinezhad
authors.affiliation: Department of Pharmacology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Panjehshahin
authors.affiliation: Nephrology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Simin
authors.initials: S
authors.lastname: Torabinezhad
authors.affiliation: Autoimmune Diseases Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Eskandar
authors.initials: E
authors.lastname: Kamali-Sarvestani
authors.affiliation: Department of Immunology, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Shirin
authors.initials: S
authors.lastname: Farjadian
authors.affiliation: Department of Pharmacology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Fatema
authors.initials: F
authors.lastname: Pirsalami
authors.affiliation: Department of Pharmacology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran; Nanomedicine and Nanobiology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Leila
authors.initials: L
authors.lastname: Moezi
keywords: Cyclosporine; Edaravone; Kidney diseases; Nitric oxide; eNOSe; iNOS