الفهرس | Only 14 pages are availabe for public view |
Abstract Drug induced cardio-toxicity is considered as one of the major concerns that lead to late stage compound failure, post- marketing drug withdrawal and restrict on drug usage. Indeed drug interactions could exaggerate cardio-toxicities and limit the efficacy of other clinically useful medicines. Pioglitazone is an antidiabetic drug belonging to thiazolidinedione family which exhibited safety problems which lead to withdrawal of some family members to avoid pertained cardiotoxicity. Both fluconazole and Itraconazole are effective oral antifungal agents and well tolerated in the management of widespread or resistant dermatomycoses. However, these agents differ markedly in their potential to cause clinically significant drug interactions. Accordingly, the aim of the present work was designed to investigate and compare the cardiotoxic potential of the anti-diabetic drug, pioglitazone and two of antifungal drugs; fluconazole and itraconazole individually or along with each other in rats.assigned into six groups of 10 rats per group. The first group was kept as control and received the vehicle (0.25% tween 80/distilled water, orally). Three groups of animals received a single treatment, either pioglitazone (10 mg/kg), fluconazole (20 mg/kg) or itraconazole (18 mg/kg). Animals of the fifth group received pioglitazone (10 mg/ kg) in combination with fluconazole (20 mg/kg) treatment, while the sixth group received combined pioglitazone (10 mg/kg) along with itraconazole treatment (18 mg/kg); all drugs were orally administrated for 28 consecutive days. At the end of experiment, rats were anesthetized and electrocardiographs (ECG) were recorded for morphological and statistical analysis of heart rate, R-R interval, R amplitude and QT prolongation in addition, blood was collected for determination of serum cardiac biomarkers, Creatine kinase-MB (CK-MB), and troponin T (cTnT) levels |