The Cardioprotective Effect of Olive leaf extract against Cardiotoxicity Induced by Carfilzomib. Modulation of cardiac biomarkers, oxidative stress, inflammation and histopathological damage

Author(s): Nabaa Ali Abd Alradha Al_Saeedi
Date: 09/10/2026
doi: https://doi.org/10.5281/zenodo.8425890

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Abstract

Background: Carfilzomib is a powerful proteasome inhibitor that is a broad-spectrum therapy used for 
multiple myeloma but may be clinically accompanied by cardiotoxicity. There was a need to investigate 
the protective effect of olive leaf extract against the cardiac toxicity caused by carfilzomib in male albino 
rats and to compare its effect with carvedilol in this study. Methodology: Thirty-six rats were randomly 
assigned to six groups: control group, group treated with olive leaf extract (400 mg/kg), group treated with 
carfilzomib, two groups where rats were treated with olive leaf extract (200 or 400 mg/kg) before they 
were treated with carfilzomib, and a group treated with carvedilol before carfilzomib. b. Cardiac damage 
markers, inflammatory markers, oxidative stress markers, and histopathological changes were then 
evaluated at the end of the experiment. Results: Administration of carfilzomib caused a marked increase 
(p < 0.05) in serum levels of troponin-I, CK-MB, LDH, TNF-α, and IL-6 as compared to the control group. 
In addition, the content of malondialdehyde (MDA) was found to be elevated in cardiac tissue with a 
significant decrease in reduced glutathione (GSH) level and superoxide dismutase (SOD) activity. The 
histopathological analysis showed severe myocardial damage with the presence of edema, vascular 
congestion, inflammatory cell infiltration, hemorrhage, myofibrillar fragmentation, and cardiomyocyte 
degeneration. The administration of olive leaf extract at a preventive level was very effective in reducing 
these biochemical and histological changes, depending on the dose. The higher dose (400 mg/kg) showed 
better protection than the lower dose (200 mg/kg), with the results showing an improvement in cardiac 
biomarkers, a reduction in inflammatory responses, restoration of antioxidant defense, and preservation 
of myocardial architecture. The cardioprotective effect was most significant in the group that was treated 
with carvedilol before the treatment Finally, olive leaf extract protected against cardiotoxicity associated 
with carfilzomib administration, which was probably due to antioxidant and anti-inflammatory effects. 
Conclusions: While carvedilol proved to be more effective, OLE clearly exhibited significant 
cardioprotective properties and could be a potent natural preventive approach against cardio-toxic effects 
of carfilzomib.

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