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Abstract

Cardiotoxicity associated with the clinically used drugs is a global concern of safety for healthcare professionals. Various animal models have been used to study the drug-induced cardiotoxicity but the exact molecular involvement of toxicity is not much clear. Despite the recurrent occurrence of toxicities, drugs such as doxorubicin, calcium channel blockers, antiarrhythmics and immunomodulators are regularly used. Anticancer drugs mainly anthracyclines, 5-fluorouracil and cyclophosphamide exert prominent cardiotoxicity. Till date, there is only one drug approved for doxorubicin-related cardiotoxicity i.e. dexrazoxane. Few other drugs are used routinely by clinicians to reduce the severity of toxicity which includes ACE inhibitors, L-carnitine, probucol, CoQ 10 , N-acetylcysteine, Vitamin E and deferoxamine, whereas antidepressants drugs, specifically tricyclic antidepressants are potential candidates for cardiotoxicity. Calcium channel blockers, antiarrhythmic and beta receptor antagonist aggravate cardiac heart failure (CHF) and left ventricular arrhythmia. Interferons, mainly interferon-α is also associated with prominent and dose-dependant toxicity. Some other drugs like zidovudine, chloroquine, cocaine, minoxidil, ketoconazole, prostaglandin E2 and anagrelide are also reported to have cardiotoxic effects. A complication associated with the use of these drugs include hypoxia, coronary ischemia, calcium overload, oxidative stress, contractile dysfunction, left ventricular arrhythmia and cardiomyopathy.

Cyclophosphamide arrhythmogenicitytesting using human-induced pluripotent stem cell-derived cardiomyocytes

“…CP is an anti-cancer drug that is used in the treatment of rheumatoid arthritis, lupus erythematosus, multiple sclerosis, neuroblastoma, and other types of cancer and it is also used in transplantology 25 . Unfortunately, its action is often associated with cardiovascular side effects such as atrioventricular block, tachyarrhythmias, heart failure, and myocarditis when taken in high doses (i.e., 100-200 mg/kg) [1][2][3][4][5][6] . While heart failure and myocarditis are caused by metabolites of CP 8 , atrioventricular block and tachyarrhythmias might be associated with the mechanisms of arrhythmia occurrence under CP influence on a cellular level, particularly when small doses of the drug are taken (i.e., less than 100 mg/kg).…”