Abstract
Back ground: Doxorubicin is a very effective anticancer therapy of the anthracycline's family used in many pediatric and adult cancers. However, due to severe cardiotoxicity adverse effect, the uses of doxorubicin are limited. Metformin reducing basal and postprandial glucose levels. Metformin has a good treatment efficacy and safety profile in treatment of T2DM in conjunction with lifestyle modification. Metformin have a cardioprotective effect in addition to reducing basal and postprandial levels of glucose by decreasing the production of reactive oxygen species, maintaining energy homeostasis and apoptosis regulation by its activation of adenosine monophosphate-activated protein kinase. Method: Thirty-six white male rabbits randomly divided to six groups, each comprising of six rabbits. 1- Control group injected 2 ml saline single dose intraperitoneally. 2- Metformin group 300 mg/kg/daily for 14 days orally. 3- Acute doxorubicin induction group 16 mg/ kg intraperitoneally as a single dose. 4- Chronic doxorubicin induction group 4mg/kg intraperitoneally twice a week for two weeks. 5- Metformin+ acute doxorubicin induction group 16 mg/kg intraperitoneally single dose and Metformin 300 mg/kg/daily for 14 days orally, three days before doxorubicin treatment. 6- Metformin + chronic doxorubicin induction group 4 mg/kg intraperitoneally, twice a week for two weeks and Metformin 300 mg/kg/daily for 14 days orally, three days before doxorubicin treatment. Result: our results revealed the treatment with metformin significantly (p < 0.05) reduced the serum level of troponin I and MMP2 in Metformin+ acute doxorubicin induction and Metformin + chronic doxorubicin induction groups in comparison with the acute doxorubicin and chronic doxorubicin groups. Conclusion: From these results in this study, we can conclude that metformin has a cardioprotective effect against doxorubicin induced cardiotoxicity in acute and also the chronic induction by decreasing serum level of troponin I and MMP2.
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