Impact of Cerium Oxide Nanoparticles on Metabolic, Apoptotic, Autophagic and Antioxidant Changes in Doxorubicin-Induced Cardiomyopathy: Possible Underlying Mechanisms

Background: In the current study, the effects of cerium oxide nanoparticles (nanocerium; NC) on doxorubicin (DOX)-induced cardiomyopathy and its possible underlying mechanisms were addressed. Methods: ۳۲ adult male rats were allocated into ۴ groups; i) control group, ii) NC group; rats received NC (۰.۲ mg/kg, i.p., daily), iii) DOX group; rats received DOX ۴ mg/kg (۲ injections with a ۱۴-day interval), and iv) DOX+NC group as DOX but rats received NC. At the end of the experiment, ECG and ECHO recordings and assessments of the levels of cardiac enzymes (CK-MB, LDH), and myocardial oxidative stress (MDA, catalase, and GSH), the expression of LC۳ and beclin۱ (markers of autophagy), caspase۳ (marker of apoptosis) by immunohistochemistry, the expression of acetyl-CoA carboxylase alpha (ACCA) by PCR, and ۵’adenosine monophosphate-activated protein kinase (AMPK) levels in the heart tissues were performed. Results: The DOX group displayed a prolonged corrected QT interval, an increase in cardiac enzymes (CK-MB and LDH), myocardial oxidative stress (high MDA with low catalase and GSH), expression of ACCA, caspase-۳, beclin۱, and LC۳ in myocardial tissues, with reduction in myocardial AMPK levels, and myocardial contractility (low ejection fraction, and fractional shortening). On the other hand, administration of NC with DOX resulted in significant improvement of all studied parameters. Conclusions: NC offers a cardioprotective effect against DOX-induced cardiomyopathy. This effect might be due to its antioxidant and antiapoptotic effects as well as to the modulation of autophagy and metabolic dysfunctions induced by DOX in the heart tissues.

Keywords:

Autophagy , Cardiomyopathy , Cerium oxide nanoparticles , Doxorubicin , Echocardiography , Oxidative stress.