Protective effects of lemon and orange peels and olive oil on doxorubicin-induced myocardial damage via inhibition of oxidative stress and inflammation pathways

Background/aimCompounds originating from plants, especially citrus fruits and olive oil, have anti-inflammatory, cardioprotective, and antioxidant characteristics. Doxorubicin (DOX), an anthracycline antineoplastic, induces cardiotoxicity by generating free radicals. This study aimed to evaluate the...

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Main Authors: Amal I. El-Refaiy, Zainab A. Salem, Abdelnaser A. Badawy, Naief Dahran, Muhammad A. Desouky, Mohammed A. El-Magd
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-03-01
Series:Frontiers in Pharmacology
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Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2025.1506673/full
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author Amal I. El-Refaiy
Zainab A. Salem
Abdelnaser A. Badawy
Naief Dahran
Muhammad A. Desouky
Muhammad A. Desouky
Mohammed A. El-Magd
author_facet Amal I. El-Refaiy
Zainab A. Salem
Abdelnaser A. Badawy
Naief Dahran
Muhammad A. Desouky
Muhammad A. Desouky
Mohammed A. El-Magd
author_sort Amal I. El-Refaiy
collection DOAJ
description Background/aimCompounds originating from plants, especially citrus fruits and olive oil, have anti-inflammatory, cardioprotective, and antioxidant characteristics. Doxorubicin (DOX), an anthracycline antineoplastic, induces cardiotoxicity by generating free radicals. This study aimed to evaluate the cardioprotective effects of orange (OP) and lemon (LP) peels and olive oil (OO) against DOX-induced myocardial damage in rats.MethodsThirty adult male albino rats were randomly assigned to five groups, with six rats in each group. The control group was labeled Group I (Cnt), while Group II (DOX) got DOX intraperitoneally. Groups III, IV, and V were given a combination of DOX with OP, LP, or OO, respectively. After 28 days, cardiac biomarkers (AST, LDH, CK, cTnT), oxidative stress markers (NO, MDA), antioxidant enzyme activities (SOD, CAT, GPx), apoptotic genes (Bax, caspase 3, Bcl2), NFκB and inflammatory cytokines (TNFα, IL1β) were assessed. Histopathological analysis of the heart was also conducted.ResultsDOX-treated rats showed significant functional and structural cardiac damage, characterized by elevated AST, LDH, CK, cTnT, NO, MDA, Bax, caspase 3, NFκB, TNFα, IL1β and reduced SOD, CAT, GPx, and Bcl2 levels. These rats exhibited myocardial necrosis, inflammatory infiltration, mitochondrial damage, and myofibril atrophy. Treatment with OP, LP, or OO mitigated these effects, with OO providing the most substantial protection.ConclusionThese findings suggest that OP, LP, or OO can reduce DOX-induced cardiac toxicity by decreasing oxidative stress, apoptosis, and inflammation.
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spelling doaj-art-a6238bb413bc40d287ad15aafbb7c8862025-08-20T02:55:35ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-03-011610.3389/fphar.2025.15066731506673Protective effects of lemon and orange peels and olive oil on doxorubicin-induced myocardial damage via inhibition of oxidative stress and inflammation pathwaysAmal I. El-Refaiy0Zainab A. Salem1Abdelnaser A. Badawy2Naief Dahran3Muhammad A. Desouky4Muhammad A. Desouky5Mohammed A. El-Magd6Department of Agricultural Zoology and Nematology, Faculty of Agriculture (Girls), Al-Azhar University, Cairo, EgyptNutrition and Food Science Department, Faculty of Home Economics, Al-Azhar University, Cairo, EgyptDepartment of Biochemistry, Faculty of Medicine, Northern Border University, Arar, Saudi ArabiaDepartment of Basic Medical Sciences, College of Medicine, University of Jeddah, Jeddah, Saudi ArabiaDepartment of Internal Medicine, The Brooklyn Hospital Center, Brooklyn, NY, United StatesDepartment of Emergency Medicine, Faculty of Medicine, Kafrelsheikh University, Kafrelsheikh, EgyptDepartment of Anatomy and Embryology, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafrelsheikh, EgyptBackground/aimCompounds originating from plants, especially citrus fruits and olive oil, have anti-inflammatory, cardioprotective, and antioxidant characteristics. Doxorubicin (DOX), an anthracycline antineoplastic, induces cardiotoxicity by generating free radicals. This study aimed to evaluate the cardioprotective effects of orange (OP) and lemon (LP) peels and olive oil (OO) against DOX-induced myocardial damage in rats.MethodsThirty adult male albino rats were randomly assigned to five groups, with six rats in each group. The control group was labeled Group I (Cnt), while Group II (DOX) got DOX intraperitoneally. Groups III, IV, and V were given a combination of DOX with OP, LP, or OO, respectively. After 28 days, cardiac biomarkers (AST, LDH, CK, cTnT), oxidative stress markers (NO, MDA), antioxidant enzyme activities (SOD, CAT, GPx), apoptotic genes (Bax, caspase 3, Bcl2), NFκB and inflammatory cytokines (TNFα, IL1β) were assessed. Histopathological analysis of the heart was also conducted.ResultsDOX-treated rats showed significant functional and structural cardiac damage, characterized by elevated AST, LDH, CK, cTnT, NO, MDA, Bax, caspase 3, NFκB, TNFα, IL1β and reduced SOD, CAT, GPx, and Bcl2 levels. These rats exhibited myocardial necrosis, inflammatory infiltration, mitochondrial damage, and myofibril atrophy. Treatment with OP, LP, or OO mitigated these effects, with OO providing the most substantial protection.ConclusionThese findings suggest that OP, LP, or OO can reduce DOX-induced cardiac toxicity by decreasing oxidative stress, apoptosis, and inflammation.https://www.frontiersin.org/articles/10.3389/fphar.2025.1506673/fullDoxorubicincardiomyocytecitrus peelsolive oilrats
spellingShingle Amal I. El-Refaiy
Zainab A. Salem
Abdelnaser A. Badawy
Naief Dahran
Muhammad A. Desouky
Muhammad A. Desouky
Mohammed A. El-Magd
Protective effects of lemon and orange peels and olive oil on doxorubicin-induced myocardial damage via inhibition of oxidative stress and inflammation pathways
Frontiers in Pharmacology
Doxorubicin
cardiomyocyte
citrus peels
olive oil
rats
title Protective effects of lemon and orange peels and olive oil on doxorubicin-induced myocardial damage via inhibition of oxidative stress and inflammation pathways
title_full Protective effects of lemon and orange peels and olive oil on doxorubicin-induced myocardial damage via inhibition of oxidative stress and inflammation pathways
title_fullStr Protective effects of lemon and orange peels and olive oil on doxorubicin-induced myocardial damage via inhibition of oxidative stress and inflammation pathways
title_full_unstemmed Protective effects of lemon and orange peels and olive oil on doxorubicin-induced myocardial damage via inhibition of oxidative stress and inflammation pathways
title_short Protective effects of lemon and orange peels and olive oil on doxorubicin-induced myocardial damage via inhibition of oxidative stress and inflammation pathways
title_sort protective effects of lemon and orange peels and olive oil on doxorubicin induced myocardial damage via inhibition of oxidative stress and inflammation pathways
topic Doxorubicin
cardiomyocyte
citrus peels
olive oil
rats
url https://www.frontiersin.org/articles/10.3389/fphar.2025.1506673/full
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