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

Faraz Mahdizadeh; Aliakbar Fazaeli; Shiva Rahimi; Masoud Ojarudi; Pouria Sobhi; Mohammad Bahrami; Lotfollah Rezagholizadeh

doi:10.1038/s41598-025-07576-4

July 1, 2025Scientific ReportsOpen Access

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

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Why the study?

Doxorubicin has severe cardiotoxicity limiting its clinical use, and while studies suggest metformin and CoQ10 may help reduce this toxicity, their individual and combined effects warranted investigation.

Does the combination of metformin and coenzyme Q10 prevent doxorubicin-induced cardiotoxicity in male Wistar rats?

Structured PICO

Does the combination of metformin and coenzyme Q10 prevent doxorubicin-induced cardiotoxicity in male Wistar rats?

P

Population

36 male Wistar rats weighing 180–250 g and aged 8–10 weeks.

I

Intervention

Metformin 200 mg/kg and Coenzyme Q10 10 mg/kg administered daily by gavage for 7 days prior to a single 25 mg/kg intraperitoneal dose of doxorubicin.

C

Comparator

Normal saline (normal control), doxorubicin alone (injury control), metformin alone + doxorubicin, CoQ10 alone + doxorubicin, and metformin + CoQ10 without doxorubicin.

O

Outcome

Serum levels of CK-MB and LDH, and heart tissue levels of MDA, TAC, CAT, GPx, and SOD, along with histopathological changes, measured 24 hours after doxorubicin injection.surrogate

The combination of metformin and coenzyme Q10 synergistically attenuates doxorubicin-induced cardiotoxicity in rats by reducing oxidative stress and preserving myocardial tissue architecture.

Limitations

Future human studies are needed to validate optimal dosing regimens and long-term outcomes in oncological settings.

Implication

Combination may protect against DOX cardiotoxicity in rats; leaves open clinical translation and human trials.

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.