The use of doxorubicin (DOX) as an antitumor therapeutic agent is limited due to its cardiotoxic effects. Metformin (Met) and sitagliptin (Sitg) are suggested to improve cardiac function. The present study aimed to determine the potential protective effects of Met and Sitg on DOX-induced cardiotoxicity. Rats were divided into six groups: groups I, II, and III received normal saline, Met, and Sitg, respectively. Groups IV, V, and VI received DOX only, Met + DOX, and Sitg + DOX, respectively. Heart tissue was used for biochemical assays which measured cardiac reduced glutathione (GSH), thiobarbituric acid reactive substances (TBARS), and tumor necrosis factor α (TNF-α). Serum creatinine kinase (CK) and lactate dehydrogenase (LDH) were also measured. The heart apex was prepared for histological (hematoxylin and eosin) and immunohistochemical examination. Intoxication of DOX was associated with a significant elevation in serum CK-MB and LDH, reduction in cardiac GSH, and increased TBARS and TNF-α compared to the controls. Administration of Met or Sitg to DOX-intoxicated rats suppressed serum CK-MB and LDH. Moreover, cardiac GSH was elevated with decreased TBARS and TNF-α. These results were confirmed by histological study. Met and Sitg caused inhibition of caspase 3 and upregulation of B-cell lymphoma 2 (Bcl-2) expression in DOX-intoxicated animals. Sitg was found to exert a significantly better protective effect compared to that of Met. It was concluded that Sitg might be more effective than Met in reducing myocardial injury in DOX-induced cardiotoxicity in rats.
Keywords: Metformin; cardiotoxicity; doxorubicin; sitagliptin.