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Recent studies established that metformin (MET), an oral antidiabetic drug, possesses an antioxidant activity. However, whether it can protect against DOX-induced energy starvation and mitochondrial damage has not been reported. Our results, in a rat model of DOX-induced cardiotoxicity, show that DOX treatment significantly increased serum levels of LDH and CK-MB, indicators of cardiac injury, and induced expression of hypertrophic gene markers. DOX also caused marked decreases in the cardiac levels of glutathione, CoA-SH and ATP, and mRNA expression of catalase and NQO-1. These biochemical changes were associated with myocardial histopathological and ultrastructural deteriorations, as observed by light and electron microscopy, respectively. Cotreatment with MET (500\u2009mg\/kg) eliminated all DOX-induced biochemical, histopathological, and ultrastructural changes. These findings demonstrate that MET successfully prevents DOX-induced cardiotoxicity<jats:italic>in vivo<\/jats:italic>by inhibiting DOX-induced oxidative stress, energy starvation, and depletion of intramitochondrial CoA-SH.<\/jats:p>","DOI":"10.1155\/2012\/434195","type":"journal-article","created":{"date-parts":[[2012,5,10]],"date-time":"2012-05-10T21:02:38Z","timestamp":1336683758000},"page":"1-13","source":"Crossref","is-referenced-by-count":59,"title":["Metformin Rescues the Myocardium from Doxorubicin-Induced Energy Starvation and Mitochondrial Damage in Rats"],"prefix":"10.1155","volume":"2012","author":[{"given":"Abdelkader E.","family":"Ashour","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. 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