At therapeutic dose, loperamide is a safe over-the-counter antidiarrheal drug but could induce cardiotoxic effect at a supratherapeutic dose. In this study, we use cardiac and oxidative biomarkers to evaluate loperamide-induced cardiotoxicity in rats. Rats were orally gavaged with 1.5, 3, or 6 mg/kg body weight (BW) of loperamide hydrochloride for 7 days. The results after 7 days administration of loperamide, revealed dose-dependent increase (P < 0.05) in aspartate aminotransferase, lactate dehydrogenase, creatine kinase-MB, and serum concentration of cardiac troponin I, total homocysteine, and nitric oxide. A 50% decrease in antioxidant enzymes activity was observed at 6 mg/kg BW. Furthermore, malondialdehyde and fragmented DNA also increased significantly in the heart of the treatment groups. Loperamide provoked cardiotoxicity through oxidative stress, lipid peroxidation, and DNA fragmentation in rats. This study has provided a possible biochemical explanation for the reported cardiotoxicity induced by loperamide overdose.
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