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Primary Protection of Diosmin Against Doxorubicin Cardiotoxicity via Inhibiting Oxido-Inflammatory Stress and Apoptosis in Rats

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Abstract

Doxorubicin (DOX) is the cornerstone of chemotherapy. However, it has dose-dependent cardiotoxic events that limit its clinical use. This study was intended to investigate the efficiency of DOX as an anti-cancer against the MCF-7 cell line in the presence of diosmin (DIO) and to appraise the protective impact of DIO against DOX cardiotoxicity in vivo. In vitro study was carried out to establish the conservation of DOX cytotoxicity in the presence of DIO. In vivo study was conducted on 42 adult female Wistar rats that were equally allocated into 6 groups; control, DIO (100 mg/kg), DIO (200 mg/kg), DOX (20 mg/kg, single dose i.p.), DIO (100 mg/kg) + DOX, received DIO orally (100 mg/kg) for 30 days, then administrated with a single dose of DOX and DIO (200 mg/kg) + DOX, received DIO orally (200 mg/kg) for 30 days, then administrated with DOX. In vitro study showed preservation of cytotoxic activity of DOX on MCF-7 in the presence of DIO. In vivo study indicated that DOX altered electrocardiograph (ECG) parameters. Also, it yielded a significant rise in CK-MB, cTnT and LDH serum levels and cardiac contents of MDA, IL-1β; paralleled by a significant drop in cardiac IL-10 and SOD. Moreover, significant upregulation of Bax, TNF-α, and HIF-1α, in concomitant with significant downregulation of Bcl-2 mRNA in cardiac tissue have been recorded in the DOX group. Furthermore, histopathological description of cardiac tissues showed that DOX alters normal cardiac histoarchitecture. On the opposite side, DIO pretreatment could ameliorate ECG parameters, suppress IL-1β and enhanceIL-10, promote activity of SOD and repress MDA. Additionally, downregulation of Bax, TNF-α, HIF-1α and upregulation of Bcl-2 have been demonstrated in DIO-pretreated rats. Furthermore, the histopathological examination of cardiac tissues illustrated that DIO had a favorable impact on the protection of heart histoarchitecture. DIO is suggested for protection against acute cardiotoxicity caused by DOX without affecting antitumor activity.

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Authors and Affiliations

  1. Hormones Department, Medical Research and Clinical Studies Institute, National Research Centre, Giza, Egypt

    Rehab S. Abohashem, Hanaa H. Ahmed & Alaa H. Sayed

  2. Stem Cell Laboratory, Centre of Excellence for Advanced Sciences, National Research Centre, Giza, Egypt

    Rehab S. Abohashem & Hanaa H. Ahmed

  3. Medical Biochemistry and Molecular Biology Unit, Department of Cancer Biology, National Cancer Institute, Cairo University, Cairo, Egypt

    Heba Effat

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  2. Hanaa H. Ahmed
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  3. Alaa H. Sayed
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  4. Heba Effat
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Contributions

Rehab S. Abohashem conceived and designed the idea, performed the in vivo study and participated in the biochemical and data analysis, and wrote the manuscript. Hanaa H. Ahmed conceived and designed the idea, revised the manuscript, and provided the administrative support. Alaa H. Sayed participated in the biochemical and data analysis. Heba Effat performed the in vitro study and molecular genetic analysis, participated in data analysis and writing the manuscript. All the authors have read and approved the final manuscript.

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Correspondence to Rehab S. Abohashem.

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The authors declare no competing interests.

Ethical Approval

The experimental protocol was conducted in compliance with the National Institute of Health guidelines and with the approval of Institutional Ethical Committee for Medical Research, National Research Centre, Egypt (Code No. 62311122022).

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Abohashem, R.S., Ahmed, H.H., Sayed, A.H. et al. Primary Protection of Diosmin Against Doxorubicin Cardiotoxicity via Inhibiting Oxido-Inflammatory Stress and Apoptosis in Rats. Cell Biochem Biophys (2024). https://doi.org/10.1007/s12013-024-01289-7

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