Key result
Chitosan-conjugated doxorubicin plus propionic acid reduces cardiotoxicity and restores cardiac biomarkers and ECG parameters.
Why the study?
Doxorubicin is an extensively prescribed antineoplastic agent known for adverse cardiotoxicity, prompting investigation into underlying mechanisms and strategies to reduce toxicity.
Does conjugation of doxorubicin with chitosan nanoparticles and supplementation with propionic acid reduce cardiotoxicity in a rat model?
Does conjugation of doxorubicin with chitosan nanoparticles and supplementation with propionic acid reduce cardiotoxicity in a rat model?
Conjugating doxorubicin with chitosan nanoparticles and providing propionic acid supplementation may mitigate doxorubicin-induced cardiotoxicity via PPARγ upregulation.
Should not alter doxorubicin regimens; hypothesis-generating for nanoparticle cardioprotection in animal models.
Doxorubicin is an extensively prescribed antineoplastic agent. It is also known for adverse effects, among which cardiotoxicity tops the list. The possible mechanism underlying doxorubicin (DOX)-mediated cardiotoxicity has been investigated in this study. Further, to reduce the DOX-mediated cardiotoxicity, DOX was conjugated with Chitosan Nanoparticles (DCNPs) and supplemented with propionic acid. Initially, the drug loading efficacy and conjugation of DOX with chitosan was confirmed by UV-Visible Spectroscopy (UV) and Fourier Transform Infrared Spectroscopy (FTIR). The average sizes of the synthesized Chitosan Nanoparticles (CNPs) and DCNPs were measured by Dynamic Light Scattering (DLS) analysis as 187.9 ± 1.05 nm and 277.3 ± 8.15 nm, respectively, and the zeta potential values were recorded as 55.2 ± 0.7 mV and 51.9 ± 1.0 mV, respectively. The size and shape of CNPs and DCNPs were recorded using a High-Resolution Electron Microscopy (HRTEM). The particles measured <30 nm and 33-84 nm, respectively. The toxic effects of DCNPs and propionic acid were evaluated in rat model. The data from the electrocardiogram (ECG), cardiac biomarkers, Peroxisome proliferator-activated receptor gamma (PPARγ) and histological observations indicated evidence of DOX-mediated cardiotoxicity, whereas the administration of DCNPs, as well as Propionic Acid (PA), brought about a restoration to normalcy and offered protection in the context of DOX-induced cardiotoxicity.
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Siva et al. (2022) studied Doxorubicin-induced cardiotoxicity (n=35). Doxorubicin conjugated with chitosan nanoparticles (DCNPs) and propionic acid (PA) vs. Doxorubicin alone (10 mg/kg cumulative dose) was evaluated on Cardiotoxicity assessed by ECG, cardiac biomarkers, oxidative stress markers, and PPARγ expression. Conjugation of doxorubicin with chitosan nanoparticles and supplementation with propionic acid reduced doxorubicin-induced cardiotoxicity by restoring normal cardiac biomarkers, ECG parameters, and upregulating PPARγ expression.
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