Metabolomics Of Metformin's Cardioprotective Effect In Acute Doxorubicin Induced- Cardiotoxicity In Rats

Doxorubicin (DOX) is a powerful anticancer agent with sever cardiotoxic side effect which limits the clinical use. Metformin (MET) is antihyperglycemic drug with potential cardioprotective effect via AMP-activated protein kinase (AMPK) (increases fatty acid oxidation, decreases the production of ROS, maintaining energy homeostasis and apoptosis). Metabolomics technology deals with systematic study of chemical fingerprints of metabolite profiles. Different metabolic processes can be identified which will give information of any change in the metabolic profile of tissues as well as of biofluids after drug administration. This research designed to investigate MET cardioprotective effect against acute cardiotoxicity induced by DOX using metabolomics technology. Methods: Twenty four adult male wistar rats divided into four groups (6 animals each): control group (saline, i.p.); MET group (300mg/kg/day for 7dayes) by gavage; DOX group (20 mg/kg,i.p.) for acute induction of cardiotoxicity; Met + DOX group received DOX (20mg/kg i.p.) and Met (300 mg/kg/day, for 7 days, starting five days prior to DOX treatment) orally with gavage. Assessment of heart tissue metabolomics, serum MDA and GSH in addition to trichrome stain. Results: The results showed that pretreatment with MET (MET+DOX) significantly (p