Skip to main content

Advertisement

SpringerLink
Log in

Protective Effect of Curcumin, Chrysin and Thymoquinone Injection on Trastuzumab-Induced Cardiotoxicity via Mitochondrial Protection

  • Published:
Cardiovascular Toxicology Aims and scope Submit manuscript

Abstract

Mitochondrial dysfunction may lead to cardiomyocyte death in trastuzumab (TZM)-induced cardiotoxicity. Accordingly, this study was designed to evaluate the mitochondrial protective effects of curcumin, chrysin and thymoquinone alone in TZM-induced cardiotoxicity in the rats. Forty-eight male adult Wistar rats were divided into eight groups: control group (normal saline), TZM group (2.5 mg/kg I.P. injection, daily), TZM + curcumin group (10 mg/kg, I.P. injection, daily), TZM + chrysin (10 mg/kg, I.P. injection, daily), TZM + thymoquinone (0.5 mg/kg, I.P. injection, daily), curcumin group (10 mg/kg, I.P. injection, daily), chrysin group (10 mg/kg, I.P. injection, daily) and thymoquinone group (10 mg/kg, I.P. injection, daily). Blood and tissue were collected on day 11 and used for assessment of creatine phosphokinase, lactate dehydrogenase (LDH), troponin, malondialdehyde (MDA) amount, glutathione levels and mitochondrial toxicity parameters. TZM increased mitochondrial impairments (reactive oxygen species formation, mitochondrial swelling, mitochondrial membrane potential collapse and decline in succinate dehydrogenase activity) and histopathological alterations (hypertrophy, enlarged cell, disarrangement, myocytes degeneration, infiltration of fat in some areas, hemorrhage and focal vascular thrombosis) in rat heart. As well as TZM produced a significant increase in the level of CK, LDH, troponin, MDA, glutathione disulfide. In most experiments, the co-injection of curcumin, chrysin and thymoquinone with TZM restored the level of CK, LDH, troponin, MDA, GSH, mitochondrial impairments and histopathological alterations. The study revealed the cardioprotective effects of curcumin, chrysin and thymoquinone against TZM-induced cardiotoxicity which could be attributed to their antioxidant and mitochondrial protection activities.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Data Availability

The datasets pertaining to this research is available from the corresponding author on reasonable request.

References

  1. Spector, N. L., & Blackwell, K. L. (2009). Understanding the mechanisms behind trastuzumab therapy for human epidermal growth factor receptor 2–positive breast cancer. Journal of Clinical Oncology, 27, 5838–5847.

    Article  CAS  PubMed  Google Scholar 

  2. Nami, B., Maadi, H., & Wang, Z. (2018). Mechanisms underlying the action and synergism of trastuzumab and pertuzumab in targeting HER2-positive breast cancer. Cancers, 10, 342.

    Article  CAS  PubMed Central  Google Scholar 

  3. Moilanen, T., Jokimäki, A., Tenhunen, O., & Koivunen, J. P. (2018). Trastuzumab-induced cardiotoxicity and its risk factors in real-world setting of breast cancer patients. Journal of Cancer Research and Clinical Oncology, 144, 1613–1621.

    Article  CAS  PubMed  Google Scholar 

  4. Nowsheen, S., Aziz, K., Park, J. Y., Lerman, A., Villarraga, H. R., Ruddy, K. J., et al. (2018). Trastuzumab in female breast cancer patients with reduced left ventricular ejection fraction. Journal of the American Heart Association, 7, e008637.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Mohan, N., Jiang, J., Dokmanovic, M., & Wu, W. J. (2018). Trastuzumab-mediated cardiotoxicity: Current understanding, challenges, and frontiers. Antibody therapeutics, 1, 13–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Nowsheen, S., Viscuse, P. V., O’Sullivan, C. C., Sandhu, N. P., Haddad, T. C., Blaes, A., et al. (2017). Incidence, diagnosis, and treatment of cardiac toxicity from trastuzumab in patients with breast cancer. Current Breast Cancer Reports, 9, 173–182.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Gabani, M., Castañeda, D., Nguyen, Q. M., Choi, S.-K., Chen, C., Mapara, A., et al. (2021). Association of cardiotoxicity with doxorubicin and trastuzumab: A double-edged sword in chemotherapy. Cureus, 13, e18194.

    PubMed  PubMed Central  Google Scholar 

  8. Xu, Y., Li, X., Liu, X., & Zhou, M. (2010). Neuregulin-1/ErbB signaling and chronic heart failure. Advances in Pharmacology, 59, 31–51.

    Article  CAS  PubMed  Google Scholar 

  9. El-Gamal, M. I., Mewafi, N. H., Abdelmotteleb, N. E., Emara, M. A., Tarazi, H., Sbenati, R. M., et al. (2021). A review of HER4 (ErbB4) kinase, its impact on cancer, and its inhibitors. Molecules, 26, 7376.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Gorini, S., De Angelis, A., Berrino, L., Malara, N., Rosano, G., & Ferraro, E. (2018). Chemotherapeutic drugs and mitochondrial dysfunction: focus on doxorubicin, trastuzumab, and sunitinib. Oxidative Medicine and Cellular Longevity, 2018, 1–15.

    Article  CAS  Google Scholar 

  11. Li, A., Gao, M., Jiang, W., Qin, Y., & Gong, G. (2020). Mitochondrial dynamics in adult cardiomyocytes and heart diseases. Frontiers in Cell and Developmental Biology, 8, 1555.

    Google Scholar 

  12. Dorn, G. W., II. (2013). Mitochondrial dynamics in heart disease. Biochimica et Biophysica Acta (BBA)—Molecular Cell Research, 1833, 233–241.

    Article  CAS  Google Scholar 

  13. Lochner, A., Wang, H.-H., Reiter, R. J., Guo, R., & Zhou, H. (2021). Role of mitochondrial quality control in myocardial and microvascular physiology and pathophysiology. Frontiers in Physiology, 12, 1495.

    Article  Google Scholar 

  14. Kornfeld, O. S., Hwang, S., Disatnik, M.-H., Chen, C.-H., Qvit, N., & Mochly-Rosen, D. (2015). Mitochondrial reactive oxygen species at the heart of the matter: New therapeutic approaches for cardiovascular diseases. Circulation Research, 116, 1783–1799.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Sun, L., Wang, H., Yu, S., Zhang, L., Jiang, J., & Zhou, Q. (2022). Herceptin induces ferroptosis and mitochondrial dysfunction in H9c2 cells. International Journal of Molecular Medicine, 49, 1–8.

    PubMed  Google Scholar 

  16. Varga, Z. V., Ferdinandy, P., Liaudet, L., & Pacher, P. (2015). Drug-induced mitochondrial dysfunction and cardiotoxicity. American Journal of Physiology-Heart and Circulatory Physiology, 309, H1453–H1467.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Barish, R., Gates, E., & Barac, A. (2019). Trastuzumab-induced cardiomyopathy. Cardiology Clinics, 37, 407–418.

    Article  PubMed  Google Scholar 

  18. Stéphane, F. F. Y., Jules, B. K. J., Batiha, G.E.-S., Ali, I., & Bruno, L. N. (2021). Extraction of bioactive compounds from medicinal plants and herbs. London: InTech Open.

    Google Scholar 

  19. Shah, S. M. A., Akram, M., Riaz, M., Munir, N., & Rasool, G. (2019). Cardioprotective potential of plant-derived molecules: A scientific and medicinal approach. Dose-Response, 17, 1559325819852243.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Sharifi-Rad, M., Anil Kumar, N. V., Zucca, P., Varoni, E. M., Dini, L., Panzarini, E., et al. (2020). Lifestyle, oxidative stress, and antioxidants: back and forth in the pathophysiology of chronic diseases. Frontiers in Physiology, 11, 694.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Farkhondeh, T., Samarghandian, S., & Bafandeh, F. (2019). The cardiovascular protective effects of chrysin: a narrative review on experimental researches. Cardiovascular & Hematological Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Cardiovascular & Hematological Agents), 17, 17–27.

    Article  CAS  Google Scholar 

  22. Yarmohammadi, F., Hayes, A. W., & Karimi, G. (2021). Protective effects of curcumin on chemical and drug-induced cardiotoxicity: A review. Naunyn-Schmiedeberg’s Archives of Pharmacology, 394, 1341–1353.

    Article  CAS  PubMed  Google Scholar 

  23. Liu, H., Liu, H. Y., Jiang, Y. N., & Li, N. (2016). Protective effect of thymoquinone improves cardiovascular function, and attenuates oxidative stress, inflammation and apoptosis by mediating the PI3K/Akt pathway in diabetic rats. Molecular Medicine Reports, 13, 2836–2842.

    Article  CAS  PubMed  Google Scholar 

  24. Jakubczyk, K., Drużga, A., Katarzyna, J., & Skonieczna-Żydecka, K. (2020). Antioxidant potential of curcumin—a Meta-analysis of randomized clinical trials. Antioxidants, 9, 1092.

    Article  CAS  PubMed Central  Google Scholar 

  25. Kohandel, Z., Farkhondeh, T., Aschner, M., & Samarghandian, S. (2021). Anti-inflammatory effects of thymoquinone and its protective effects against several diseases. Biomedicine & Pharmacotherapy, 138, 111492.

    Article  CAS  Google Scholar 

  26. Khezri, S., Sabzalipour, T., Jahedsani, A., Azizian, S., Atashbar, S., & Salimi, A. (2020). Chrysin ameliorates aluminum p hosphide-induced oxidative stress and mitochondrial damages in rat cardiomyocytes and isolated mitochondria. Environmental Toxicology, 35, 1114–1124.

    Article  CAS  PubMed  Google Scholar 

  27. Sahebkar, A., Serban, M.-C., Ursoniu, S., & Banach, M. (2015). Effect of curcuminoids on oxidative stress: A systematic review and meta-analysis of randomized controlled trials. Journal of functional foods, 18, 898–909.

    Article  CAS  Google Scholar 

  28. Mani, R., & Natesan, V. (2018). Chrysin: Sources, beneficial pharmacological activities, and molecular mechanism of action. Phytochemistry, 145, 187–196.

    Article  CAS  PubMed  Google Scholar 

  29. Tabassum, S., Rosli, N., Ichwan, S. J. A., & Mishra, P. (2021). Thymoquinone and its pharmacological perspective: A review. Pharmacological Research-Modern Chinese Medicine, 1, 100020.

    Article  Google Scholar 

  30. Ghareghomi, S., Rahban, M., Moosavi-Movahedi, Z., Habibi-Rezaei, M., Saso, L., & Moosavi-Movahedi, A. A. (2021). The potential role of curcumin in modulating the master antioxidant pathway in diabetic hypoxia-induced complications. Molecules, 26, 7658.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Hasanuzzaman, M., Bhuyan, M., Zulfiqar, F., Raza, A., Mohsin, S. M., Mahmud, J. A., et al. (2020). Reactive oxygen species and antioxidant defense in plants under abiotic stress: Revisiting the crucial role of a universal defense regulator. Antioxidants, 9, 681.

    Article  CAS  PubMed Central  Google Scholar 

  32. Sabet, N. S., Atashbar, S., Khanlou, E. M., Kahrizi, F., & Salimi, A. (2020). Curcumin attenuates bevacizumab-induced toxicity via suppressing oxidative stress and preventing mitochondrial dysfunction in heart mitochondria. Naunyn-Schmiedeberg’s Archives of Pharmacology, 393, 1447–1457.

    Article  CAS  PubMed  Google Scholar 

  33. Hafez, A. A., Jamali, Z., Khezri, S., & Salimi, A. (2021). Thymoquinone reduces mitochondrial damage and death of cardiomyocytes induced by clozapine. Naunyn-Schmiedeberg’s Archives of Pharmacology, 394, 1675–1684.

    Article  CAS  PubMed  Google Scholar 

  34. Olorundare, O., Adeneye, A., Akinsola, A., Soyemi, S., Mgbehoma, A., Okoye, I., et al. (2020). African vegetables (Clerodendrum volubile Leaf and Irvingia gabonensis seed extracts) effectively mitigate trastuzumab-induced cardiotoxicity in wistar rats. Oxidative Medicine and Cellular Longevity, 2020, 1–15.

    Google Scholar 

  35. Ahmadabady, S., Beheshti, F., Shahidpour, F., Khordad, E., & Hosseini, M. (2021). A protective effect of curcumin on cardiovascular oxidative stress indicators in systemic inflammation induced by lipopolysaccharide in rats. Biochemistry and Biophysics Reports, 25, 100908.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Zhai, K., Hu, L., Chen, J., Fu, C.-Y., & Chen, Q. (2008). Chrysin induces hyperalgesia via the GABAA receptor in mice. Planta Medica, 74, 1229–1234.

    Article  CAS  PubMed  Google Scholar 

  37. Olorundare, O. E., Adeneye, A. A., Akinsola, A. O., Ajayi, A. M., Agede, O. A., Soyemi, S. S., et al. (2021). Therapeutic potentials of selected antihypertensive agents and their fixed-dose combinations against trastuzumab-mediated cardiotoxicity. Frontiers in Pharmacology, 11, 2160.

    Article  CAS  Google Scholar 

  38. Nabofa, W. E., Alashe, O. O., Oyeyemi, O. T., Attah, A. F., Oyagbemi, A. A., Omobowale, T. O., et al. (2018). Cardioprotective effects of curcumin-nisin based poly lactic acid nanoparticle on myocardial infarction in guinea pigs. Scientific Reports, 8, 1–11.

    Article  CAS  Google Scholar 

  39. Iacobellis, G., Corradi, D., & Sharma, A. M. (2005). Epicardial adipose tissue: Anatomic, biomolecular and clinical relationships with the heart. Nature Clinical Practice Cardiovascular medicine, 2, 536–543.

    Article  PubMed  Google Scholar 

  40. Fraga, C. G., Leibovitz, B. E., & Tappel, A. L. (1988). Lipid peroxidation measured as thiobarbituric acid-reactive substances in tissue slices: Characterization and comparison with homogenates and microsomes. Free Radical Biology and Medicine, 4, 155–161.

    Article  CAS  PubMed  Google Scholar 

  41. Ellman, G. L., & Gan, G. L. (1964). Erythrocyte glutathione-levels in patients of a mental hospital. Nature, 202, 904–904.

    Article  CAS  PubMed  Google Scholar 

  42. Djafarzadeh, S., & Jakob, S. M. (2017). Isolation of intact mitochondria from skeletal muscle by differential centrifugation for high-resolution respirometry measurements. JoVE (Journal of Visualized Experiments). https://doi.org/10.3791/55251

  43. Salimi, A., Minouei, M., Niknejad, M., & Mojarad Aylar, E. (2021). Antioxidant activity of calcitriol reduces direct methamphetamine-induced mitochondrial dysfunction in isolated rat heart mitochondria. Toxin Reviews. https://doi.org/10.1080/15569543.2021.1978499

    Article  Google Scholar 

  44. Mattiasson, G. (2004). Analysis of mitochondrial generation and release of reactive oxygen species. Cytometry Part A: The Journal of the International Society for Analytical Cytology, 62, 89–96.

    Article  CAS  Google Scholar 

  45. Cottet-Rousselle, C., Ronot, X., Leverve, X., & Mayol, J. F. (2011). Cytometric assessment of mitochondria using fluorescent probes. Cytometry Part A, 79, 405–425.

    Article  CAS  Google Scholar 

  46. Pentassuglia, L., & Sawyer, D. B. (2009). The role of Neuregulin-1β/ErbB signaling in the heart. Experimental Cell Research, 315, 627–637.

    Article  CAS  PubMed  Google Scholar 

  47. Geissler, A., Ryzhov, S., & Sawyer, D. B. (2020). Neuregulins: Protective and reparative growth factors in multiple forms of cardiovascular disease. Clinical Science, 134, 2623–2643.

    Article  CAS  PubMed  Google Scholar 

  48. Onitilo, A. A., Engel, J. M., & Stankowski, R. V. (2014). Cardiovascular toxicity associated with adjuvant trastuzumab therapy: Prevalence, patient characteristics, and risk factors. Therapeutic Advances in Drug Safety, 5, 154–166.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Lai, L., & Qiu, H. (2020). The physiological and pathological roles of mitochondrial calcium uptake in heart. International Journal of Molecular Sciences, 21, 7689.

    Article  CAS  PubMed Central  Google Scholar 

  50. Lin, M., Xiong, W., Wang, S., Li, Y., Hou, C., Li, C., et al. (2021). The research progress of trastuzumab-induced cardiotoxicity in HER-2-positive breast cancer treatment. Frontiers in Cardiovascular Medicine. https://doi.org/10.3389/fcvm.2021.821663

    Article  PubMed  PubMed Central  Google Scholar 

  51. Zeglinski, M., Ludke, A., Jassal, D. S., & Singal, P. K. (2011). Trastuzumab-induced cardiac dysfunction: A ‘dual-hit.’ Experimental & Clinical Cardiology, 16, 70.

    CAS  Google Scholar 

  52. Mailloux, R. J. (2020). An update on mitochondrial reactive oxygen species production. Antioxidants, 9, 472.

    Article  CAS  PubMed Central  Google Scholar 

  53. Goszcz, K., Deakin, S. J., Duthie, G. G., Stewart, D., Leslie, S. J., & Megson, I. L. (2015). Antioxidants in cardiovascular therapy: Panacea or false hope? Frontiers in Cardiovascular Medicine, 2, 29.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  54. Angsutararux, P., Luanpitpong, S., & Issaragrisil, S. (2015). Chemotherapy-induced cardiotoxicity: overview of the roles of oxidative stress. Oxidative Medicine and Cellular Longevity, 2015, 1–13.

    Article  CAS  Google Scholar 

  55. Tang, H., Zhao, J., Feng, R., Pu, P., & Wen, L. (2022). Reducing oxidative stress may be important for treating pirarubicin-induced cardiotoxicity with schisandrin B. Experimental and Therapeutic Medicine, 23, 1–8.

    Google Scholar 

  56. D’Oria, R., Schipani, R., Leonardini, A., Natalicchio, A., Perrini, S., Cignarelli, A., et al. (2020). The role of oxidative stress in cardiac disease: from physiological response to injury factor. Oxidative Medicine and Cellular Longevity, 2020, 1–29.

    Article  CAS  Google Scholar 

  57. Ye, B., Ling, W., Wang, Y., Jaisi, A., & Olatunji, O. J. (2022). Protective effects of chrysin against cyclophosphamide-induced cardiotoxicity in rats: A biochemical and histopathological approach. Chemistry & Biodiversity. https://doi.org/10.1002/cbdv.202100886

    Article  Google Scholar 

  58. Mantawy, E. M., El-Bakly, W. M., Esmat, A., Badr, A. M., & El-Demerdash, E. (2014). Chrysin alleviates acute doxorubicin cardiotoxicity in rats via suppression of oxidative stress, inflammation and apoptosis. European Journal of Pharmacology, 728, 107–118.

    Article  CAS  PubMed  Google Scholar 

  59. Naik, S. R., Thakare, V. N., & Patil, S. R. (2011). Protective effect of curcumin on experimentally induced inflammation, hepatotoxicity and cardiotoxicity in rats: Evidence of its antioxidant property. Experimental and Toxicologic Pathology, 63, 419–431.

    Article  CAS  PubMed  Google Scholar 

  60. Bahadır, A., Ceyhan, A., Gergin, Ö. Ö., Yalçın, B., Ülger, M., Özyazgan, T. M., et al. (2018). Protective effects of curcumin and beta-carotene on cisplatin-induced cardiotoxicity: An experimental rat model. Anatolian Journal of Cardiology, 19, 213.

    PubMed  PubMed Central  Google Scholar 

  61. Chakraborty, M., Bhattacharjee, A., & Kamath, J. V. (2017). Cardioprotective effect of curcumin and piperine combination against cyclophosphamide-induced cardiotoxicity. Indian Journal of Pharmacology, 49, 65.

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Alam, M. F., Khan, G., Safhi, M. M., Alshahrani, S., Siddiqui, R., Sivagurunathan Moni, S., et al. (2018). Thymoquinone ameliorates doxorubicin-induced cardiotoxicity in Swiss Albino mice by modulating oxidative damage and cellular inflammation. Cardiology Research and Practice, 2018, 1–6.

    Article  Google Scholar 

  63. Karabulut, D., Ozturk, E., Kaymak, E., Akin, A. T., & Yakan, B. (2021). Thymoquinone attenuates doxorubicin-cardiotoxicity in rats. Journal of Biochemical and Molecular Toxicology, 35, e22618.

    Article  CAS  PubMed  Google Scholar 

  64. Bagheri, H., Ghasemi, F., Barreto, G. E., Rafiee, R., Sathyapalan, T., & Sahebkar, A. (2020). Effects of curcumin on mitochondria in neurodegenerative diseases. BioFactors, 46, 5–20.

    Article  CAS  PubMed  Google Scholar 

  65. Kicinska, A., & Jarmuszkiewicz, W. (2020). Flavonoids and mitochondria: Activation of cytoprotective pathways? Molecules, 25, 3060.

    Article  CAS  PubMed Central  Google Scholar 

  66. Khalifa, A. A., Rashad, R. M., & El-Hadidy, W. F. (2021). Thymoquinone protects against cardiac mitochondrial DNA loss, oxidative stress, inflammation and apoptosis in isoproterenol-induced myocardial infarction in rats. Heliyon, 7, e07561.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Su, X., Zhou, M., Li, Y., Zhang, J., An, N., Yang, F., et al. (2022). Protective effects of natural products against myocardial ischemia/reperfusion: Mitochondria-targeted therapeutics. Biomedicine & Pharmacotherapy, 149, 112893.

    Article  CAS  Google Scholar 

  68. Ojha, S., Al Taee, H., Goyal, S., Mahajan, U. B., Patil, C. R., Arya, D., et al. (2016). Cardioprotective potentials of plant-derived small molecules against doxorubicin associated cardiotoxicity. Oxidative Medicine and Cellular Longevity, 2016, 1–19.

    Google Scholar 

  69. Yang, Y., Wei, S., Zhang, B., & Li, W. (2021). Recent progress in environmental toxins-induced cardiotoxicity and protective potential of natural products. Frontiers in Pharmacology, 12, 1733.

    Google Scholar 

  70. Swamy, A. V., Gulliaya, S., Thippeswamy, A., Koti, B. C., & Manjula, D. V. (2012). Cardioprotective effect of curcumin against doxorubicin-induced myocardial toxicity in albino rats. Indian Journal of Pharmacology, 44, 73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Izem-Meziane, M., Djerdjouri, B., Rimbaud, S., Caffin, F., Fortin, D., Garnier, A., et al. (2012). Catecholamine-induced cardiac mitochondrial dysfunction and mPTP opening: Protective effect of curcumin. American Journal of Physiology-Heart and Circulatory Physiology, 302, H665–H674.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This study was supported by Ardabil University of Medical Sciences, Deputy of Research (Grant No. IR.ARUMS.REC.1399.637).

Author information

Author notes

  1. Mohammad Shabani has contributed equally with Leila Rezaie Shirmard.

Authors and Affiliations

  1. Department of Pharmaceutics, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran

    Leila Rezaie Shirmard

  2. Department of Pharmacology and Toxicology, School of Pharmacy, Ardabil University of Medical Sciences, P.O. Box: 56189-53141, Ardabil, Iran

    Mohammad Shabani, Amin Ashena Moghadam, Nasim Zamani, Hadi Ghanbari & Ahmad Salimi

  3. Traditional Medicine and Hydrotherapy Research Center, Ardabil University of Medical Sciences, Ardabil, Iran

    Ahmad Salimi

Authors
  1. Leila Rezaie Shirmard
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mohammad Shabani
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Amin Ashena Moghadam
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nasim Zamani
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hadi Ghanbari
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ahmad Salimi
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

LRS and MS contributed to the manuscript. MS, AAM, NZ and HG performed the experiments. AS conceptualized the study, analyzed and interpreted the data, drafted and revised the manuscript. All the authors read and approved the final manuscript.

Corresponding author

Correspondence to Ahmad Salimi.

Ethics declarations

Conflict of interest

Authors declare that he has no conflict of interest.

Ethical Approval

All experiments were performed based on standard protocols approved by the Ethic Committee of Ardabil University of Medical Sciences (Ethic Code: IR.ARUMS.REC.1399.637).

Consent to Participate

Not applicable.

Consent to Publish

Not applicable.

Additional information

Handling Editor: Y. Robert Li.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shirmard, L.R., Shabani, M., Moghadam, A.A. et al. Protective Effect of Curcumin, Chrysin and Thymoquinone Injection on Trastuzumab-Induced Cardiotoxicity via Mitochondrial Protection. Cardiovasc Toxicol 22, 663–675 (2022). https://doi.org/10.1007/s12012-022-09750-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12012-022-09750-w

Keywords

Search

Navigation