Please use this identifier to cite or link to this item: http://hdl.handle.net/10316/4705
Title: Oxidative Stress in Cyclosporine-Induced Hypertension: Evidence of Beneficial Effects or Tolerance Development With Nitrate Therapy
Authors: Reis, F. 
Rocha-Pereira, P. 
Lemos, E. Teixeira de 
Parada, B. 
Baptista, S. 
Figueiredo, A. 
Santos-Silva, A. 
Costa-Almeida, C. 
Mota, A. 
Teixeira, F. 
Issue Date: 2007
Citation: Transplantation Proceedings. 39:8 (2007) 2494-2500
Abstract: The aim of this study was to evaluate the effect of cyclosporine (CsA) on oxidative stress as well as the use of a nitric oxide (NO) donor, the organic nitrate isosorbide-5-mononitrate (Is-5-Mn), to prevent or reverse CsA-induced toxicity, namely on the vascular NO-cGMP pathway or on oxidative equilibrium. The following rat groups (n = 8) were tested: (1) a control group; (2) the CsA group (5 mg/kg/d for 7 weeks); (3) the Is-5-Mn group (150 mg/kg/d, twice a day for 7 weeks); (4) the preventive group (Is-5-Mn + CsA) treated for 2 weeks with Is-5-Mn only, and thereafter with both drugs for 7 weeks; (5) the curative group (CsA + Is-5-Mn) beginning 7 weeks after CsA, and following thereafter with both drugs for 5 weeks. The following parameters were evaluated: aortic cNOS activity and cGMP content; plasma levels of lipid peroxidation (malondialdehyde [MDA] levels); antioxidant capacity (glutathione peroxidase [GPx] and superoxide dismutase [SOD] activities, total antioxidant status, and vitamins A, C, and E); and peroxynitrite formation (3-nitrotyrosine [3-NT] content). Is-5-Mn + CsA therapy showed, when compared with the CsA group, total prevention of CsA-induced NO and cGMP attenuation, and no relevant influence on antioxidant indices, as well as on MDA and 3-NT levels. However, when compared with this CsA group, the curative group (CsA + Is-5-Mn) showed NO-cGMP values only partially reversed, and an enhancement in lipid peroxidation (5.6 ± 1.4 vs 12.78 ± 3.63 [mu]mol/L; P < .05) and in peroxynitrite formation (16.7% incidence of positives vs 83.3% incidence of positives). Our data suggested that nitrate therapy may provide a valid choice to prevent CsA-induced NO-cGMP decrease, without a negative influence on the oxidative equilibrium. However, when the local environment is adverse, as occurs after CsA therapy, Is-5-Mn seemed to enhance the CsA-induced oxidative stress, promoting even worse deleterious effects, probably through the generation of the cytotoxic ROS peroxynitrite.
URI: http://hdl.handle.net/10316/4705
DOI: 10.1016/j.transproceed.2007.07.030
Rights: openAccess
Appears in Collections:FMUC Medicina - Artigos em Revistas Internacionais

Files in This Item:
File Description SizeFormat
file4f6d3d03a48d4f77be39a527ae1dec56.pdf379.93 kBAdobe PDFView/Open
Show full item record

SCOPUSTM   
Citations

16
checked on Nov 17, 2022

WEB OF SCIENCETM
Citations

15
checked on Nov 15, 2022

Page view(s)

297
checked on Nov 21, 2022

Download(s) 50

429
checked on Nov 21, 2022

Google ScholarTM

Check

Altmetric

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.