A Chemosensitizer Drug: Disulfiram Prevents Doxorubicin-Induced Cardiac Dysfunction and Oxidative Stress in Rats

A Chemosensitizer Drug: Disulfiram Prevents Doxorubicin-Induced Cardiac Dysfunction and Oxidative Stress in Rats

In the present study, the preventive effects of orally administered disulfiram (DS) against the doxorubicin (DOX)-induced cardiotoxicity were investigated in rats. DS was orally administered for 7 days at doses of 2, 10, and 50 mg/kg/day. DOX (30 mg/kg) was intraperitoneally administered on the 5th...

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Bibliographic Details
Published in:Cardiovascular toxicology Vol. 18; no. 5; pp. 459 - 470
Main Authors: Sonawane, Varsha K., Mahajan, Umesh B., Shinde, Sachin D., Chatterjee, Subhajit, Chaudhari, Sandip S., Bhangale, Harshada A., Ojha, Shreesh, Goyal, Sameer N., Kundu, Chanakya N., Patil, Chandragouda R.
Format: Journal Article
Language:English
Published: New York Springer US 01-10-2018
Springer
Springer Nature B.V
Subjects:
Antimitotic agents
Antineoplastic agents
Antioxidants
Biomedical and Life Sciences
Biomedicine
Cancer
Cardiology
Cardiotoxicity
Catalase
Chemosensitization
Chemotherapy
Creatine
Creatine kinase
Disulfiram
Doxorubicin
Edema
EKG
Enzymes
Glutathione
Heart
Heart diseases
Injection
Injury prevention
L-Lactate dehydrogenase
Lactate dehydrogenase
Lactic acid
Lipid peroxidation
Myocardium
Myonecrosis
NF-κB protein
Nitric oxide
Oral administration
Oxidative stress
Peroxidation
Pharmacology/Toxicology
Prevention
Rats
Serum levels
ST-height
Disulfiram
Oxidative stress
TNF-α
Doxorubicin
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Summary:In the present study, the preventive effects of orally administered disulfiram (DS) against the doxorubicin (DOX)-induced cardiotoxicity were investigated in rats. DS was orally administered for 7 days at doses of 2, 10, and 50 mg/kg/day. DOX (30 mg/kg) was intraperitoneally administered on the 5th day of the initiation of DS treatment. Within 48 h of injection, DOX treatment significantly altered ECG, elevated the ST height, and increased the QT and QRS intervals. It reduced the cardiac levels of injury markers like creatine kinase isoenzyme-MB and lactate dehydrogenase. DOX elevated the serum levels of SGOT and nitric oxide. Its injection significantly induced lipid peroxidation in the cardiac tissue and reduced the activities of innate antioxidants like super oxide dismutase, catalase, and reduced glutathione in the cardiac tissue. DOX treatment raised the TNF-α level and caused histological alterations in the myocardium like neutrophil infiltrations, myonecrosis, and edema. Pre-treatment of rats with DS (2, 10, and 50 mg/kg p. o. for 7 days) prevented the ECG changes, minimized oxidative stress, and normalized the biochemical indicators of the DOX-induced cardiotoxicity. DS also protected rat heart from DOX-induced histological alterations. Recently, DS is reported to exert chemosensitization of cancer cells. Our in vitro investigation using MCF7 cell line revealed that DS reverses the DOX-induced suppression of NF-κB and Nrf2 expression. These findings about the protective activity of DS against the DOX-induced cardiotoxicity warrant a detailed investigation on its utility as an adjunct therapy to cancer chemotherapy.
ISSN:1530-7905
1559-0259
DOI:10.1007/s12012-018-9458-y