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Metformin Attenuates Doxorubicin‐induced Cardiotoxicity In Rats
Author(s) -
AlHaider Abdlqader A.,
Korashy Hesham M.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1038.3
Subject(s) - cardiotoxicity , doxorubicin , lactate dehydrogenase , pharmacology , medicine , creatine kinase , glutathione , metformin , antioxidant , chemotherapy , chemistry , enzyme , biochemistry , endocrinology , diabetes mellitus
The clinical use of doxorubicin (DOX), a potent chemotherapeutic agent, is limited by its cardiotoxic side effects that are attributed to free radical generation. Recent studies have established that metformin (MET), an oral antidiabetic drug, possesses an antioxidant activity. However, whether it can protect against DOX‐induced cardiotoxicity has not been reported before. The goal of the present study was to assess the extent to which MET can prevent cardiotoxicity induced by DOX. Results of our study in a rat model of DOX‐induced cardiotoxicity show that DOX treatment caused significant increases in serum levels of lactate dehydrogenase (LDH) and creatine phosphokinase isoenzyme MB (CK‐MB), indicators of cardiac injury. In addition, DOX therapy decreased cardiac glutathione, an endogenous antioxidant; CoA‐SH, an activator in mitochondrial energy providing systems. These biochemical changes were associated with myocardial histopathological and ultrastructural deteriorations. Co‐treatment with MET eliminated all DOX‐induced increases of LDH and CK‐MB and prevented GSH, CoA‐SH and ATP depletions. MET therapy also prevented all the myocardial histopathological and ultrastructural deteriorations. These findings demonstrate, that MET successfully prevents DOX‐induced cardiotoxicity.