Role of hesperidin/hesperetin against chemotherapy-induced cardiotoxicity: a systematic review of non-clinical studies

Abstract Despite the undeniable role of chemotherapeutics in cancer treatment, their administration may be associated with various side effects. Cardiac injury is among the most crucial side effects related to the induction of chemotherapeutic agents. Since the heart is a vital organ, cardiotoxicity...

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Main Authors: Sina Shaernejad, Ali Nosrat, Maryam Baeeri, Nasser Hashemi Goradel, Mirsalim SeyedSadeghi, Mostafa Akbariani, AmirAhmad Arabzadeh, Mahban Rahimifard, Hamed Haghi-Aminjan
Format: Article
Language:English
Published: BMC 2025-05-01
Series:Cancer Cell International
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Online Access:https://doi.org/10.1186/s12935-025-03828-5
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author Sina Shaernejad
Ali Nosrat
Maryam Baeeri
Nasser Hashemi Goradel
Mirsalim SeyedSadeghi
Mostafa Akbariani
AmirAhmad Arabzadeh
Mahban Rahimifard
Hamed Haghi-Aminjan
author_facet Sina Shaernejad
Ali Nosrat
Maryam Baeeri
Nasser Hashemi Goradel
Mirsalim SeyedSadeghi
Mostafa Akbariani
AmirAhmad Arabzadeh
Mahban Rahimifard
Hamed Haghi-Aminjan
author_sort Sina Shaernejad
collection DOAJ
description Abstract Despite the undeniable role of chemotherapeutics in cancer treatment, their administration may be associated with various side effects. Cardiac injury is among the most crucial side effects related to the induction of chemotherapeutic agents. Since the heart is a vital organ, cardiotoxicity often prevents clinicians from continuing chemotherapy. Hesperidin and hesperetin, flavonoids derived from citrus fruits, possess several pharmaceutical properties. This study firstly explores the cardioprotective effects of hesperidin and hesperetin against chemotherapy-induced cardiotoxicity mechanisms, emphasizing their potential as adjunctive therapies. Key literature gaps are identified, and further mechanistic studies will be proposed. The findings underscore the translational potential of these flavonoids, advocating for rigorous preclinical optimization and clinical trials to validate their efficacy and safety. This review lays a foundation for integrating natural compounds into cardioprotective strategies in oncology. A systematic search was conducted in databases (PubMed, Scopus, ISI) until May 2025, according to PRISMA principles. The search terms were chosen according to our research objective and queried in the title and abstract. Following the screening of 82 papers, twelve articles were selected based on our inclusion and exclusion criteria. Based on the evaluated results, chemotherapy adversely affects cardiac tissue, leading to elevated risks of morbidity and mortality. Co-administration of hesperidin and hesperetin with chemotherapy prevents heart injury and preserves cardiac function, maintaining it almost like a normal heart. The protective role of hesperidin and hesperetin is based on their ability to fight free radicals, reduce inflammation, and stop cell death. Nonclinical investigations indicate that hesperidin and hesperetin ameliorate chemotherapy-induced cardiotoxicity. Nonetheless, they may influence the efficacy of anticancer medications, which primarily function by elevating oxidants, inflammation, and apoptosis. This indicates that meticulously designed trials are necessary to evaluate the efficacy and safety of this combination along with the synergistic potential of them in preventing chemotherapy-induced cardiotoxicity while maintaining anticancer effectiveness.
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spelling doaj-art-729b67027d9d4cfbb9aff993e6e7e5a02025-08-20T03:08:44ZengBMCCancer Cell International1475-28672025-05-0125111310.1186/s12935-025-03828-5Role of hesperidin/hesperetin against chemotherapy-induced cardiotoxicity: a systematic review of non-clinical studiesSina Shaernejad0Ali Nosrat1Maryam Baeeri2Nasser Hashemi Goradel3Mirsalim SeyedSadeghi4Mostafa Akbariani5AmirAhmad Arabzadeh6Mahban Rahimifard7Hamed Haghi-Aminjan8Students Research Committee, School of Medicine, Ardabil University of Medical SciencesStudents Research Committee, School of Medicine, Ardabil University of Medical SciencesToxicology and Diseases Specialty Group, Pharmaceutical Sciences Research Center (PSRC), Tehran University of Medical Sciences (TUMS)Department of Medical Biotechnology, Maragheh University of Medical SciencesDepartment of Surgery, School of Medicine, Ardabil University of Medical SciencesDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical SciencesDepartment of Surgery, School of Medicine, Ardabil University of Medical SciencesToxicology and Diseases Specialty Group, Pharmaceutical Sciences Research Center (PSRC), Tehran University of Medical Sciences (TUMS)Toxicology and Diseases Specialty Group, Pharmaceutical Sciences Research Center (PSRC), Tehran University of Medical Sciences (TUMS)Abstract Despite the undeniable role of chemotherapeutics in cancer treatment, their administration may be associated with various side effects. Cardiac injury is among the most crucial side effects related to the induction of chemotherapeutic agents. Since the heart is a vital organ, cardiotoxicity often prevents clinicians from continuing chemotherapy. Hesperidin and hesperetin, flavonoids derived from citrus fruits, possess several pharmaceutical properties. This study firstly explores the cardioprotective effects of hesperidin and hesperetin against chemotherapy-induced cardiotoxicity mechanisms, emphasizing their potential as adjunctive therapies. Key literature gaps are identified, and further mechanistic studies will be proposed. The findings underscore the translational potential of these flavonoids, advocating for rigorous preclinical optimization and clinical trials to validate their efficacy and safety. This review lays a foundation for integrating natural compounds into cardioprotective strategies in oncology. A systematic search was conducted in databases (PubMed, Scopus, ISI) until May 2025, according to PRISMA principles. The search terms were chosen according to our research objective and queried in the title and abstract. Following the screening of 82 papers, twelve articles were selected based on our inclusion and exclusion criteria. Based on the evaluated results, chemotherapy adversely affects cardiac tissue, leading to elevated risks of morbidity and mortality. Co-administration of hesperidin and hesperetin with chemotherapy prevents heart injury and preserves cardiac function, maintaining it almost like a normal heart. The protective role of hesperidin and hesperetin is based on their ability to fight free radicals, reduce inflammation, and stop cell death. Nonclinical investigations indicate that hesperidin and hesperetin ameliorate chemotherapy-induced cardiotoxicity. Nonetheless, they may influence the efficacy of anticancer medications, which primarily function by elevating oxidants, inflammation, and apoptosis. This indicates that meticulously designed trials are necessary to evaluate the efficacy and safety of this combination along with the synergistic potential of them in preventing chemotherapy-induced cardiotoxicity while maintaining anticancer effectiveness.https://doi.org/10.1186/s12935-025-03828-5DoxorubicinPaclitaxelCisplatinCyclophosphamideEpirubicin
spellingShingle Sina Shaernejad
Ali Nosrat
Maryam Baeeri
Nasser Hashemi Goradel
Mirsalim SeyedSadeghi
Mostafa Akbariani
AmirAhmad Arabzadeh
Mahban Rahimifard
Hamed Haghi-Aminjan
Role of hesperidin/hesperetin against chemotherapy-induced cardiotoxicity: a systematic review of non-clinical studies
Cancer Cell International
Doxorubicin
Paclitaxel
Cisplatin
Cyclophosphamide
Epirubicin
title Role of hesperidin/hesperetin against chemotherapy-induced cardiotoxicity: a systematic review of non-clinical studies
title_full Role of hesperidin/hesperetin against chemotherapy-induced cardiotoxicity: a systematic review of non-clinical studies
title_fullStr Role of hesperidin/hesperetin against chemotherapy-induced cardiotoxicity: a systematic review of non-clinical studies
title_full_unstemmed Role of hesperidin/hesperetin against chemotherapy-induced cardiotoxicity: a systematic review of non-clinical studies
title_short Role of hesperidin/hesperetin against chemotherapy-induced cardiotoxicity: a systematic review of non-clinical studies
title_sort role of hesperidin hesperetin against chemotherapy induced cardiotoxicity a systematic review of non clinical studies
topic Doxorubicin
Paclitaxel
Cisplatin
Cyclophosphamide
Epirubicin
url https://doi.org/10.1186/s12935-025-03828-5
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