title: Ozone-Oxidative Preconditioning Prevents Doxorubicin-induced Cardiotoxicity in Sprague-Dawley Rats.
abstract: OBJECTIVE
  Induced dilated cardiomyopathy is the main limitation of the anti-cancer drug doxorubicin, which causes oxidative stress and cardiomyocyte death. As ozone therapy can activate the antioxidant systems, this study aimed to investigate the therapeutic efficacy of ozone-oxidative preconditioning against doxorubicin-induced cardiotoxicity.
  
  
  METHODS
  The study was carried out from September 2013 to January 2014. Sprague-Dawley rats were randomly distributed in the following treatment groups: Group 1 were treated with 2 mg/kg intraperitoneal (i.p.) of doxorubicin twice a week for 50 days; Group 2 were treated with 0.3 mg of ozone/oxygen mixture at 50 μg/mL of ozone per 6 mL of oxygen by rectal insufflation and then treated with doxorubicin; Group 3 were treated as Group 2 but only with the oxygen, and Group 4 were treated with oxygen first, and then with sodium chloride i.p. as the control group.
  
  
  RESULTS
  The results showed that ozone therapy preserved left ventricle morphology which was accompanied by a reduction of serum pro-brain natriuretic peptide levels. The cardioprotective effects of ozone-oxidative preconditioning were associated with a significant increase (P <0.05) of antioxidant enzymes activities and a reduction of lipid and protein oxidation (P <0.05).
  
  
  CONCLUSIONS
  Ozone-oxidative preconditioning prevents doxorubicin-induced dilated cardiomyopathy through an increase of antioxidant enzymes and a reduction of oxidised macromolecules. This establishes the background for future studies to determine if ozone therapy can be used as a complementary treatment for attenuating doxorubicin-induced cardiotoxicity in cancer patients.
authors.affiliation: Center of Studies for Research & Biological Evaluations, Pharmacy & Food Science College, University of Havana, Cuba;
authors.forename: Livan
authors.initials: L
authors.lastname: Delgado-Roche
authors.affiliation: Center of Studies for Research & Biological Evaluations, Pharmacy & Food Science College, University of Havana, Cuba;
authors.forename: Yanet
authors.initials: Y
authors.lastname: Hernández-Matos
authors.affiliation: Center of Studies for Research & Biological Evaluations, Pharmacy & Food Science College, University of Havana, Cuba;
authors.forename: Emilio A
authors.initials: EA
authors.lastname: Medina
authors.affiliation: Center of Studies for Research & Biological Evaluations, Pharmacy & Food Science College, University of Havana, Cuba;
authors.forename: Dalia Á
authors.initials: DÁ
authors.lastname: Morejón
authors.affiliation: LABIOFAM Pharmaceutical Laboratories, Havana, Cuba;
authors.forename: Maité R
authors.initials: MR
authors.lastname: González
authors.affiliation: Medical Center Beauty Benefit, Osimo, Ancona, Italy.
authors.forename: Gregorio
authors.initials: G
authors.lastname: Martínez-Sánchez
keywords: Cardiotoxins; Dilated Cardiomyopathy; Doxorubicin; Oxidative Stress; Ozone
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