Abstract

Objective: Drug-drug interactions could augment or develop cardiotoxicities. Drug induced cardiotoxicityconsidered one of the major concerns that lead to serious and life threatening clinical situations The current study was carried out to investigate and compare the innate cardiotoxic potential of pioglitazone, an antidiabetic drug, and selected azole antifungals e.g. fluconazole / itraconazole in non-diabetic healthy rats either administrated alone or concomitantly.

Method: Adult male Sprague dawely ratsrandomly and equally assigned into six groups 10 rats each. The first was kept as control and received the vehicle (0.25% tween 80/distilled water), three groups were received single drug treatment;pioglitazone at (10 mg/kg), fluconazole at (20 mg/kg) and Itraconazole at (18 mg/kg). While animals of fifth group-received co-treatments of pioglitazone (10 mg/kg) and fluconazole (20 mg/kg) and animals of sixth group received combination of pioglitazone (10 mg/kg) and itraconazole (18 mg/kg).all drugs were administrated orally for 28 consecutive days.

Results: single drug treatments induced morphological electrocardiographical (ECG) changes,elevated serumCreatine kinase-MB (CK-MB),elevated serum troponin-T (cTnT) except fluconazole, elevated tissue GSH, diminished catalase activity (CAT) and only single fluconazole and pioglitazone showed elevation in cardiacmalondialdehyde (MDA).Single azoles showed significant increase in apoptotic marker caspase-3, while combined treatments showed morphological ECG changes, prolonged QTc interval, elevation of CK-MB and cTnT, elevated GSH and diminished CAT activity.

Conclusion: Pioglitazone and azole antifungals have the potential to develop cardiomyopathical and electrophysiological toxicity in healthy rats either single or combined.