title: Efficacy of amifostine in protection against doxorubicin-induced acute cardiotoxic effects in rats.
abstract: OBJECTIVE
  Amifostine (AMI) is a broad-spectrum cytoprotector which protects against variety of radio- and chemotherapy-related toxicities without decreasing their antitumor action. The aim of the study was to investigate the potential protective effects of AMI against acute cardiotoxic effects of doxorubicin (DOX) in male Wistar rats.
  
  
  METHODS
  AMI (300 mg/kg ip) was given 30 min before DOX (6 mg/kg and 10mg/kg b.w., iv). The evaluation of DOX-induced cardiotoxic effects, as well as cardioprotective efficacy of AMI was performed 48 h after their administration by determining serum activities of enzymes known to be markers of cardiac damage (creatine kinase - CK, aspartate aminotransferase - AST, lactate dehydrogenase - LDH, and its isoenzyme alpha-hydroxybutirate dehydrogenase - alpha - HBDH), as well as the histopathological and ultrastructural analysis of the heart tissue.
  
  
  RESULTS
  AMI successfully prevented a significant increase in serum activity of CK, AST, LDH and alpha-HBDH in animals treated with DOX in the dose of 6 mg/kg (121.14 +/- 18.37 vs 167.70 +/- 44.24; 771.42 +/- 161.99 vs 1057.00 +/- 300.00; 3230.00 +/- 1031.73 vs 4243.10 +/- 904.06; 202.57 +/- 42.46 vs 294.90 +/- 80.20 UI/l, respectively), and ameliorated DOX-induced structural damage of the rat myocardium. Pretreatment with AMI in rats given 10 mg/kg DOX reduced the cardiac damage score (CDS) from 2.62 +/- 0.51 to 1.62 +/- 0.51, i.e. to the CDS value obtained with the lower dose of DOX (6 mg/kg). The ultrastructural analysis of the rat myocardium showed that AMI successfully protected the sarcolemma of cardiomyocytes and reduced mitochondria damage induced by DOX given in the dose of 6 mg/kg. Besides, capillaries were less morphologically changed and apoptosis of endothelial cells was extremely rare in AMI-protected animals. AMI itself did not cause any prominent changes in the examined parameters in comparison with the control rats.
  
  
  CONCLUSIONS
  AMI provided a significant protection against DOX-induced acute cardiotoxic effects in rats. This finding implies its potential to be a successful cardioprotector in patients treated with DOX due to malignant diseases.
authors: Center for Clinical Pharmacology, Institute for Scientific Information, Belgrade, Serbia. vdragsim@gmail.com
authors: Viktorija
authors: V
authors: Dragojević-Simić
authors: Silva
authors: S
authors: Dobrić
authors: Vesna
authors: V
authors: Jaćević
authors: Dubravko
authors: D
authors: Bokonjić
authors: Ivica
authors: I
authors: Milosavljević
authors: Aleksandra
authors: A
authors: Kovacević
authors: Dragan
authors: D
authors: Mikić
mesh_terms: D004999:Amifostine / Q000627:therapeutic use*; D000818:Animals; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D004317:Doxorubicin / Q000633:toxicity*; D006321:Heart / Q000187:drug effects*; D008297:Male; D009206:Myocardium / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002316:Cardiotonic Agents; D004317:Doxorubicin; D004999:Amifostine