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. 2025 Jul 1;15(1):20725.
doi: 10.1038/s41598-025-07576-4.

Combined effects of metformin and coenzyme Q10 on doxorubicin-induced cardiotoxicity in male wistar rats

Faraz Mahdizadeh  1 , Aliakbar Fazaeli  2 , Shiva Rahimi  3 , Masoud Ojarudi  4 , Pouria Sobhi  1 , Mohammad Bahrami  1 , Lotfollah Rezagholizadeh  5
Affiliations

Combined effects of metformin and coenzyme Q10 on doxorubicin-induced cardiotoxicity in male wistar rats

Faraz Mahdizadeh et al. Sci Rep. .

Abstract

Doxorubicin (DOX) is an effective anticancer drug, but its clinical application is limited due to its severe adverse effects on multiple organs and tissues, particularly cardiotoxicity. Studies suggest that metformin and Coenzyme Q10 (CoQ10) may help reduce DOX-induced cardiotoxicity. This study investigated the individual and combined effects of metformin and CoQ10 on DOX-induced cardiotoxicity in rats. 36 male Wistar rats were divided into six groups consisting of N_C, C_Dox (25 mg/kg DOX), C_(Met + Q10) (200 mg/kg metformin + 10 mg/kg CoQ10), T_Met (200 mg/kg metformin + 25 mg/kg DOX), T_Q10 (10 mg/kg CoQ10 + 25 mg/kg DOX), and T_(Met + Q10) (200 mg/kg metformin + 10 mg/kg CoQ10 + 25 mg/kg DOX). DOX administration significantly elevated serum CK-MB, LDH (P < 0.05), and tissue MDA (P < 0.001). It also significantly decreased TAC, CAT, GPx (P < 0.001), and SOD (P < 0.01) in heart tissues. Treatment with metformin and CoQ10 significantly restored the biochemical parameters both in the serum and tissue samples and ameliorated the histopathological damage caused by DOX. In conclusion, the combination of metformin and CoQ10 exerted antioxidant and cardioprotective effects against DOX-induced cardiotoxicity.

Keywords: Cardioprotection; Cardiotoxicity; Coenzyme Q10; Doxorubicin; Metformin.

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Conflict of interest statement

Declarations. Competing interests: The authors declare no competing interests. Conflict of interest: The authors report no conflicts of interest. Ethical approval: This study was approved by the Ardabil University of Medical Sciences (Ethics code: IR.ARUMS.AEC.1402.004).

Figures

Fig. 1
Fig. 1
A summary of the study design is shown above. N_C; normal control group, C_(Met + Q10); metformin and CoQ10 control group, C_Dox; DOX injury control group, T_Met; metformin pre-treatment group, T_Q10; CoQ10 pre-treatment group, T_(Met + Q10); Pre-treatment group with combination of metformin and CoQ10.
Fig. 2
Fig. 2
The effect of pre-treatment with metformin and coenzyme Q10 on MDA levels of rats treated with DOX. Data is expressed as mean ± standard error. ### represents a significant difference between N_C and C_Dox groups (p < 0. 001). *** represents a significant difference between C_Dox and T_Met groups (p < 0.001). *** represents a significant difference between C_Dox and T_Q10 as well as C_Dox and T_(Met + Q10) groups (p < 0.001). N_C: Normal Control; C_(Met + Q10): metformin and coenzyme Q10 control group; C_Dox: DOX control group; T_Met: metformin test group; T_Q10: coenzyme Q10 test group; T_(Met + Q10): metformin and coenzyme Q10 test group; MDA: malondialdehyde.
Fig. 3
Fig. 3
The effect of pre-treatment with metformin and coenzyme Q10 on TAC of rats treated with DOX. Data is expressed as mean ± standard error. ### represents a significant difference between N_C and C_Dox groups (p < 0.001). *** represents a significant difference between C_Dox and T_Q10, as well as C_Dox and T_(Met + Q10) groups (p < 0.0001). N_C: Normal Control; C_(Met + Q10): metformin and coenzyme Q10 control group; C_Dox: DOX control group; T_Met: metformin test group; T_Q10: coenzyme Q10 test group; T_(Met + Q10): metformin and coenzyme Q10 test group; TAC: total antioxidant capacity.
Fig. 4
Fig. 4
The effect of pre-treatment with metformin and coenzyme Q10 on the CAT activity of rats treated with DOX. Data is expressed as mean ± standard error. ### indicates a significant difference between N_C and C_Dox groups (p < 0. 001). *** indicates a significant difference between C_Dox and T_(Met + Q10) groups (p < 0.001). N_C: Normal Control; C_(Met + Q10): metformin and coenzyme Q10 control group; C_Dox: DOX control group; T_Met: metformin test group; T_Q10: coenzyme Q10 test group; T_(Met + Q10): metformin and coenzyme Q10 test group; TAC: total antioxidant capacity.
Fig. 5
Fig. 5
The effect of pre-treatment with metformin and coenzyme Q10 on tissue SOD activity of rats treated with DOX. Data is expressed as mean ± standard error. ## indicates a significant difference between N_C and C_Dox groups (p < 0.01). * Indicates a significant difference between C_Dox and T_Met groups (p < 0.05). **indicates a significant difference between C_Dox and T_(Met + Q10) groups (p < 0.01). N_C: Normal Control; C_(Met + Q10): metformin and coenzyme Q10 control group; C_Dox: DOX control group; T_Met: metformin test group; T_Q10: coenzyme Q10 test group; T_(Met + Q10): metformin and coenzyme Q10 test group; TAC: total antioxidant capacity.
Fig. 6
Fig. 6
The effect of pre-treatment with metformin and coenzyme Q10 on tissue GPx activity of rats treated with DOX. Data is expressed as mean ± standard error. ### indicates a significant difference between N_C and C_Dox groups (p < 0.001). * Indicates a significant difference between C_Dox and T_Q10 groups (p < 0.05). *** indicates a significant difference between C_Dox and T_(Met + Q10) as well as C_Dox and T_Met groups (p < 0.01). N_C: Normal Control; C_(Met + Q10): metformin and coenzyme Q10 control group; C_Dox: DOX control group; T_Met: metformin test group; T_Q10: coenzyme Q10 test group; T_(Met + Q10): metformin and coenzyme Q10 test group; GPx: glutathione peroxidase.
Fig. 7
Fig. 7
Microscopic heart tissue image in the studied groups (hematoxylin-eosin staining x40). In the N_C group (A) and the C_(Met + Q10) group (B), the normal structure of muscle fibers (1) can be seen. DOX destroyed muscle fibers (2) and pyknosis of nuclei (3) (C). Treatment of rats with metformin (D), Q10 (E), and Q10 + metformin (F) prevented DOX-induced tissue damage.
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References

    1. Ferlay, J. et al. Cancer statistics for the year 2020: an overview. Int. J. Cancer. 149, 778–789 (2021). - PubMed
    1. Curigliano, G. et al. Cardiotoxicity of anticancer treatments: epidemiology, detection, and management. Cancer J. Clin.66, 309–325 (2016). - PubMed
    1. Fitzmaurice, C. et al. Global, regional, and National cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 29 cancer groups, 1990 to 2016: a systematic analysis for the global burden of disease study. JAMA Oncol.4, 1553–1568 (2018). - PMC - PubMed
    1. Soerjomataram, I. & Bray, F. Planning for tomorrow: global cancer incidence and the role of prevention 2020–2070. Nat. Reviews Clin. Oncol.18, 663–672 (2021). - PubMed
    1. Ewer, M. S. & Ewer, S. M. Cardiotoxicity of anticancer treatments. Nat. Reviews Cardiol.12, 547–558 (2015). - PubMed

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