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The protective effect of erdosteine against cyclosporine A-induced cardiotoxicity in rats.

Abstract
Cyclosporine A (CsA) is a frequently used immunosuppressive agent in transplant medicine to prevent rejection and in the treatment of autoimmune diseases. However, CsA generates reactive oxygen species, which causes nephrotoxicity, hepatotoxicity and cardiotoxicity. The use of antioxidants reduces the adverse effects of CsA. The aim of this study is to determine the protective effects of erdosteine on CsA-induced heart injury through tissue oxidant/antioxidant parameters and light microscopic evaluation in rats. CsA cardiotoxicity was induced by administrating an oral dose of 15mg/kg CsA daily for 21 days. The rats were divided into four groups: control group (n=4), CsA administrated group (15mg/kg, n=5), CsA+erdosteine administrated group (10mg/kg day orally erdosteine, n=4) and only erdosteine administrated group (10mg/kg day orally n=5). CsA treated rats showed increase in the number of infiltrated cells and disorganization of myocardial fibers with interstitial fibrosis. The number of infiltrated cells, disorganization of myocardial fibers and interstitial fibrosis was diminished in the hearts of CsA-treated rats given erdosteine. The malondialdehyde, the protein carbonyl content and nitric oxide levels were increased in the cyclosporine A group in comparison with the control and CsA plus erdosteine groups. The activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were higher in CsA plus erdosteine group than CsA group. However, the CAT, GSH-Px and SOD activities were significantly lower in CsA group than in control group and erdosteine group. These results suggest that erdosteine has protective effect against CsA-induced cardiotoxicity.
AuthorsYusuf Selcoki, Ebru Uz, Reyhan Bayrak, Semsettin Sahin, Arif Kaya, Burak Uz, Aydin Karanfil, Adem Ozkara, Ali Akcay
JournalToxicology (Toxicology) Vol. 239 Issue 1-2 Pg. 53-9 (Sep 24 2007) ISSN: 0300-483X [Print] Ireland
PMID17689165 (Publication Type: Journal Article)
Chemical References
  • Expectorants
  • Immunosuppressive Agents
  • Thioglycolates
  • Thiophenes
  • Nitric Oxide
  • Malondialdehyde
  • erdosteine
  • Cyclosporine
  • Catalase
  • Glutathione Peroxidase
  • Superoxide Dismutase
Topics
  • Animals
  • Catalase (metabolism)
  • Chemoprevention
  • Cyclosporine (toxicity)
  • Disease Models, Animal
  • Expectorants (therapeutic use)
  • Fibrosis (chemically induced, metabolism, pathology)
  • Glutathione Peroxidase (metabolism)
  • Heart (drug effects)
  • Heart Diseases (chemically induced, pathology, prevention & control)
  • Immunosuppressive Agents (toxicity)
  • Male
  • Malondialdehyde (metabolism)
  • Myocardium (metabolism, pathology)
  • Nitric Oxide (metabolism)
  • Oxidative Stress (drug effects)
  • Protein Carbonylation (drug effects)
  • Rats
  • Rats, Wistar
  • Superoxide Dismutase (metabolism)
  • Thioglycolates (therapeutic use)
  • Thiophenes (therapeutic use)

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