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Volume 12, Issue 3 (Vol.12 No.3 Oct 2023)
rbmb.net 2023, 12(3): 495-511 |
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Elmorshdy Elsaeed Mohammed Elmorshdy S, Ahmed Shaker G, Helmy Eldken Z, Abdelbadie Salem M, Awadalla A, Mahmoud Abdel Shakour H, et al . Impact of Cerium Oxide Nanoparticles on Metabolic, Apoptotic, Autophagic and Antioxidant Changes in Doxorubicin-Induced Cardiomyopathy: Possible Underlying Mechanisms. rbmb.net 2023; 12 (3) :495-511
URL: http://rbmb.net/article-1-1199-en.html
URL: http://rbmb.net/article-1-1199-en.html
Shorouk Elmorshdy Elsaeed Mohammed Elmorshdy 
, Gehan Ahmed Shaker , Zienab Helmy Eldken , Mahmoud Abdelbadie Salem , Amira Awadalla , Hany Mahmoud Abdel Shakour , Mohammed Elmahdy El Hosiny Sarhan , Abdelaziz Mohamed Hussein *
, Gehan Ahmed Shaker , Zienab Helmy Eldken , Mahmoud Abdelbadie Salem , Amira Awadalla , Hany Mahmoud Abdel Shakour , Mohammed Elmahdy El Hosiny Sarhan , Abdelaziz Mohamed Hussein *
Medical physiology department, Faculty of Medicine, Mansoura University, Egypt.
Abstract: (408 Views)
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: 32 adult male rats were allocated into 4 groups; i) control group, ii) NC group; rats received NC (0.2 mg/kg, i.p., daily), iii) DOX group; rats received DOX 4 mg/kg (2 injections with a 14-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 LC3 and beclin1 (markers of autophagy), caspase3 (marker of apoptosis) by immunohistochemistry, the expression of acetyl-CoA carboxylase alpha (ACCA) by PCR, and 5’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-3, beclin1, and LC3 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.
Methods: 32 adult male rats were allocated into 4 groups; i) control group, ii) NC group; rats received NC (0.2 mg/kg, i.p., daily), iii) DOX group; rats received DOX 4 mg/kg (2 injections with a 14-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 LC3 and beclin1 (markers of autophagy), caspase3 (marker of apoptosis) by immunohistochemistry, the expression of acetyl-CoA carboxylase alpha (ACCA) by PCR, and 5’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-3, beclin1, and LC3 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.
Type of Article: Original Article |
Subject:
Biochemistry
Received: 2023/06/27 | Accepted: 2023/08/7 | Published: 2024/02/25
Received: 2023/06/27 | Accepted: 2023/08/7 | Published: 2024/02/25
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