Exenatide Attenuation of Cardiac Rhythm Abnormalities and Blood Pressure Changes Induced by Doxorubicin in Rats

Background and Objective: Doxorubicin (DOX) is an anthracycline antibiotic anti-neoplastic drug.The DOX clinical use is limited due to the occurrence of accumulative dose-related cardiotoxicity.The objective of study was to investigate the exenatide effects on cardiac rhythm abnormalities and BP changes induced by DOX.Methodology: Male Sprague Dawley rats were used for this study and were distributed into four groups of six animals per group.Groups 1 represented the control, while group 2 were the exenatide group.In group 3, DOX was given alone, while group 4 received a combination of exenatide and DOX.Mode of administration was by intraperitoneally (DOX 3 mg kgG 1 /every other day and exenatide 10 µg kgG 1 dayG 1 ) for 2 weeks.The DOX induced changes were assessed by recording changes in QT and QRS interval in electrocardiogram (ECG), Heart Rate (HR), Mean Arterial Pressure (MAP), Systolic Arterial Pressure (SAP) and Diastolic Arterial Pressure (DAP).Graph pad prism software was used for statistical analysis, employing Student's t-test, one way ANOVA then Dunnet Post-hoc test.Results: The DOX augmented QTc, QRS interval, deceased heart rate and increased SAP, DAP and MAP.Treatment with exenatide significantly (p<0.05)decreased QTc, QRS interval thus, reversing the changes observed in ECG.Moreover treatment with exenatide ameliorated HR abnormalities induced by DOX in reducing SAP but rather caused an increase in DAP.Conclusion: These results suggested that exenatide has the potential of mitigating cardiac rhythm changes induced by the treatment with DOX.