Morphine Enhances Doxorubicin-Induced Cardiotoxicity in the Rat

Interventions to reduce the cardiotoxicity of doxorubicin are clinically relevant. Pharmacological preconditioning mimicking ischemic preconditioning has been demonstrated with morphine and represents an acceptable clinical intervention. The purpose of this study was to examine if pretreatment in vi...

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Bibliographic Details
Published in:Cardiovascular toxicology 2014-09, Vol.14 (3), p.251-259
Main Authors: Hole, Lisa Drange, Larsen, Terje Hjalmar, Fossan, Kjell Ove, Limé, Fredrik, Schjøtt, Jan
Format: Article
Language:English
Subjects:
Animals
Antibiotics, Antineoplastic - toxicity
Antimitotic agents
Antineoplastic agents
Biomarkers
Biomedical and Life Sciences
Biomedicine
Cancer
Cardiology
Cardiotoxicity
Cardiotoxicity - pathology
Disease Models, Animal
Doxorubicin - toxicity
Drug Synergism
Heart
Heart Diseases - blood
Heart Diseases - drug therapy
Hydrogen peroxide
Hydrogen Peroxide - metabolism
Ischemia
Laboratory animals
Male
Morphine
Morphine - pharmacology
Naloxone - pharmacology
Narcotic Antagonists - pharmacology
Narcotics
Narcotics - pharmacology
Pharmacology/Toxicology
Physiology
Pilot projects
Rats
Rats, Wistar
Troponin T - blood
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Summary:Interventions to reduce the cardiotoxicity of doxorubicin are clinically relevant. Pharmacological preconditioning mimicking ischemic preconditioning has been demonstrated with morphine and represents an acceptable clinical intervention. The purpose of this study was to examine if pretreatment in vivo with morphine could reduce doxorubicin-induced cardiotoxicity ex vivo in a rat model. Wistar rats were divided into six groups and pretreated with an intraperitoneal (i.p.) injection of 3 or 10 mg/kg morphine, 1 mg/kg naloxone and saline, 1 mg/kg naloxone and 3 mg/kg morphine or saline, 60 min before excision of the heart. Biochemical indices such as troponin T (TnT) and hydrogen peroxide (H 2 O 2 ) in effluate were measured together with physiological parameters in Langendorff hearts before and after doxorubicin infusion (2 mg/mL 0.05 mL/min for 45 min). Myocardial content of doxorubicin was measured at the end of infusion. Pretreatment with morphine, irrespective of dosage, produced a significant loss in left ventricular-developed pressure and an increase of TnT and H 2 O 2 in effluate before doxorubicin infusion ( p  
ISSN:1530-7905
1559-0259
DOI:10.1007/s12012-014-9249-z