Effect of metformin and sitagliptin on doxorubicin-induced cardiotoxicity in rats: Impact of oxidative stress,inflammation,and apoptosis

Doxorubicin (dox) is a widely used antineoplastic drug whose efficacy is limited by its cardiotoxicity. the aim of this study was to investigate the possible protective role of the antidiabetic drugs metformin (250 mg/kg dissolved in dw p.o. for seven days) and sitagliptin (10 mg/kg dissolved in dw p.o. for seven days) in a model of dox-induced (single dose 15 mg/kg i.p. at the fifth day) cardiotoxicity in rats. results of our study revealed that pretreatment with metformin or sitagliptin produced significant (p < 0.05) cardiac protection manifested by a significant decrease in serum levels of ldh and ck-mb enzymes and cardiac mda and total nitrites and nitrates levels,a significant increase in cardiac sod activity,and remarkable improvement in the histopathological features as well as a significant reduction in the immunohistochemical expression of cox-2,inos,and caspase-3 enzymes as compared to dox group. these results may suggest using metformin and/or sitagliptin as preferable drugs for diabetic patients suffering from cancer and receiving dox in their chemotherapy regimen. © 2015 mina thabet kelleni et al.