Title:Natural Bioactive as a Potential Therapeutic Approach for the Management of Cyclophosphamide-induced Cardiotoxicity
Volume: 21
Issue: 29
Author(s): Ashif Iqubal, Mohd. Wasim, Mohd. Ashraf, Abul Kalam Najmi, Mansoor Ali Syed, Javed Ali and Syed Ehtaishamul Haque*
Affiliation:
- Department of Pharmacology, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062,India
Keywords:
Cardiotoxicity, Oxidative stress, Natural products, Cardiac inflammation, Apoptosis, Heart failure.
Abstract: Cyclophosphamide (CP) is an extensively used anticancer drug, but its cardiotoxic
manifestation is a major concern for its widespread clinical use. The observed cardiotoxic
attributes have been reported at the therapeutic dose and often result into a high mortality
rate and poor clinical outcome. Fall in the level of antioxidant enzymes catalase
(CAT), reduced glutathione (GSH), superoxide dismutase (SOD) generation of reactive
oxygen species (ROS), inflammatory cytokines nuclear factor kappa-light-chain enhancer
of activated B cells (NF-kB), tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-
1β), apoptotic proteins (caspases) and direct damage to myocardial tissue (histological and
ultrastructural damage) are some of the reported manifestations of cardiotoxicity. The observed
clinical attributes of CP-induced cardiotoxicity are myocarditis, hemorrhage, thrombosis,
myocardial infarction (MI), reduced ejection fraction, altered electrocardiogram
(ECG) reading and heart failure. However, unlike Daxarazasone (an adjuvant to reduce
doxorubicin-induced cardiotoxicity), no approved adjuvant is available to mitigate CPinduced
cardiotoxicity. Thus, various natural bioactives have been explored for the possible
cardioprotective effect against CP-induced cardiotoxicity. In the current manuscript, we
have discussed the clinical and preclinical aspects of CP-induced cardiotoxicity, its clinically
used combination with other anticancer drugs, and the available therapeutic regimen to
mitigate this cardiotoxicity. Further, we discussed the limitations of available synthetic
drugs used as an adjuvant and discussed various natural bioactive and their experimental
details. This manuscript's overall goal is to throw light on CP-induced cardiotoxicity and
summarize all the experimental data so that researchers working in this field may scientifically
get up-to-date information in one place.
