Protective effect of carnosine on adriamycin-induced oxidative heart damage in rats

Anadolu Kardiyol Derg. 2011 Feb;11(1):3-10. doi: 10.5152/akd.2011.003. Epub 2010 Dec 24.

Abstract

Objective: Oxidative stress is one of the major factors involved in the pathogenesis of adriamycin (ADR)-induced cardiac dysfunction. The present study examined the antioxidant protective effects of carnosine (CAR) on adriamycin-induced cardiac damage in rats.

Methods: Female Sprague Dawley rats were divided into four groups. Control (CONT, n=8, saline only i.v.); carnosine (CAR, n=8.10 mg/kg/day, i.v.); adriamycin (ADR, n=10.4 mg/kg four times every 2 days for 8 days, i.v.) alone and carnosine with adriamycin (CAR+ADR, n=10). Carnosine was given one week before adriamycin treatment and following one week with adriamycin treatment. After measurement of physiological functions, blood samples were collected for biochemical assays. The hearts were excised for hemodynamic study. Comparisons between different groups were made using ANOVA and posthoc Tukey test.

Results: Adriamycin produced evident cardiac damage revealed by; hemodynamic changes - decreased left ventricular developed pressure (p=0.01), the maximum-minimum rates of change in left ventricular pressure (± dP/dt, p=0.01), electrocardiogram (ECG) changes (elevated ST, decreased R-wave, p=0.001), cardiac injury marker changes (increased creatine kinase, lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase), plasma antioxidant enzymes activity changes (decreased superoxide dismutase, glutathione peroxidase, catalase activities, p=0.03) and lipid peroxidation (elevated malondialdehyde, p=0.05) to the control and carnosine groups. Carnosine treatment caused significant attenuation (p=0.05) of cardiac dysfunction induced by adriamycin (CAR+ADR), revealed by normalization of the ventricular function, ECG and biochemical variables.

Conclusion: An increase in oxidative stress, superoxide dismutase, glutathione peroxidase levels, catalase inactivation and cardiac dysfunction induced by adriamycin were prevented by carnosine.

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Antibiotics, Antineoplastic / toxicity*
  • Aspartate Aminotransferases / blood
  • Blood Pressure / drug effects
  • Carnosine / pharmacology
  • Carnosine / therapeutic use*
  • Catalase / blood
  • Creatine Kinase / blood
  • Doxorubicin / toxicity*
  • Electrocardiography
  • Female
  • Glutathione Peroxidase / blood
  • Heart Failure / chemically induced*
  • Heart Failure / prevention & control*
  • Heart Rate / drug effects
  • Hemodynamics / drug effects
  • L-Lactate Dehydrogenase / blood
  • Lipid Peroxidation / drug effects
  • Oxidative Stress / drug effects*
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Superoxide Dismutase / blood
  • Ventricular Dysfunction, Left / chemically induced
  • Ventricular Dysfunction, Left / prevention & control

Substances

  • Antibiotics, Antineoplastic
  • Doxorubicin
  • Carnosine
  • L-Lactate Dehydrogenase
  • Catalase
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Creatine Kinase