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

Cardiovascular Toxicology
Varsha K SonawaneChandragouda R Patil

Abstract

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 histolog...Continue Reading

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Citations

Feb 7, 2020·Naunyn-Schmiedeberg's Archives of Pharmacology·Lalit A BirariChandragouda R Patil
Jul 4, 2020·Signal Transduction and Targeted Therapy·Zhe ZhangCanhua Huang
Oct 6, 2020·Frontiers in Pharmacology·Boju SunTonghua Liu
Jan 18, 2019·Molecular and Cellular Biochemistry·Ashwini S PatilSameer N Goyal
Apr 28, 2020·Heliyon·Anish SharmaTejal Gandhi

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BETA
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MDA

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