Comparative Study of the Protective Effect of Metformin and Sitagliptin against Doxorubicin-Induced Cardiotoxicity in RatsMahmoud M Kamel1*, Lubna Omar El-Farouk2, Afaf Sayed Osman3, Omayma Anwar Khorshid3 and Mohamed EL Shabrawy-Abdo3
- *Corresponding Author:
- Mahmoud M Kamel
Department of Clinical Pathology
National Cancer Institute
Cairo University, Egypt
E-mail: [email protected]
Received date: July 31, 2017; Accepted date: August 22, 2017; Published date: August 25, 2017
Citation: Kamel MM, El-Farouk LO, Osman AS, Khorshid OA, Shabrawy-Abdo ME (2017) Comparative Study of the Protective Effect of Metformin and Sitagliptin against Doxorubicin-Induced Cardiotoxicity in Rats. Clin Pharmacol Biopharm 6:174. doi: 10.4172/2167-065X.1000174
Copyright: © 2017 Kamel MM, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Background and aim: Cancer patients treated with doxorubicin are at high risk to develop cardiotoxicity and hyperglycemia. The present study was designed to compare the effect of the two anti-hyperglycemia drugs; metformin and Sitagliptin, in the prevention of doxorubicin-induced cardiotoxicity in rats.
Methods: Cardiotoxicity was induced in male Wistar rats by intraperitoneal injection of cumulative dose of doxorubicin (15 mg/kg over 3 weeks). Metformin or sitagliptin was administrated orally concomitant with intraperitoneal doxorubicin for 3 weeks. Mean body weight, systolic blood pressure, electrocardiographic changes, serum lactate dehydrogenase and creatine kinase-myocardium band, blood glucose and cardiac malondialdhyde level, cardiac histopathological examination and in vitro cardiac contractility in response to isoprenaline were be assessed.
Results: Doxorubicin induced marked cardiotoxicity evidenced by significant deterioration in body weight, systolic blood pressure and heart rate, elevation of ST segment, prolongation of QT interval, elevation in the serum level of creatine kinase-myocardiac band and lactate dehydrogenase, blood glucose and cardiac malondialdhyde level and reduced in vitro cardiac contractility in response to isoprenaline compared to control untreated rats. These changes were associated with histopathological evidence of cardiotoxicity. Administration of either metformin or sitagliptin with doxorubicin resulted in significant improvement in all tested parameters compared with doxorubicin treated rats. Metformin treated rats showed more significant improvement in systolic blood pressure, ST segment elevation, serum enzymes, cardiac malondialdhyde, histopathological finding and in vitro cardiac contractility than sitagliptin treated rats.
Conclusion: The present study showed that metformin ameliorated doxorubicin-induced cardiotoxicity better than sitagliptin.