Protective Effect of Metformin on Doxorubicin-induced Cardiomyopathy in the Adult Male Albino Rats (Light and Electron Microscopic Study)

Background: Cancer is considered as the leading cause of death in the majority of countries all over the world. Doxorubicin belongs to anthracycline group and is widely used in cancer treatment, but cardiotoxicity is one of its serious adverse effects. Metformin, a well-known anti-diabetic drug, has cardioprotective effects and thought to protect against doxorubicin-induced cardiotoxicity.Objective: to reveal the histological and biochemical alterations in the myocardium of rats treated with doxorubicin, and to explore the impact of metformin co-treatment.Material and methods: The study was done at the Animal House, Faculty of Pharmacy, Al-Azhar University between July and September 2020. Sixty adult male albino rats were used (equally divided into 5 groups); group I: given 1ml normal saline orally every day, and also injected intraperitoneally by 1ml saline every other day for 12 days; group II: given 250 mg/kg/day of metformin orally for 12 days; group III: given 3 mg/kg of doxorubicin intraperitoneally every other day for 12 days; group IV: given 250 mg/kg/day of metformin orally and 3 mg/kg of doxorubicin intraperitoneally every other day for 12 days; group V: given 3 mg/kg of doxorubicin intraperitoneally every other day for 12 days, then left 2 months for observation from the last dose.Results: In doxorubicin group, there were severe histological changes and biochemical results showed highly elevated cardiac enzymes. These results were significantly improved in metformin co-treatment and minimally improved in withdrawal group.Conclusion: This study revealed that metformin might have a protective effect against doxorubicin-induced cardiotoxicity.