The Evaluation of the Ameliorative Effect of Montelukast Against Arsenic Trioxide-Induced Cardiotoxicity in Rats

Abstract

Background: Arsenic trioxide (As2O3) is used for treating patients with acute promyelocytic leukemia (APL). The extensive application of this drug has been limited due to its severe cardiotoxicity. Montelukast is a selective leukotriene receptor antagonist with antioxidant and anti-inflammatory properties. Objectives: This study evaluated whether montelukast could protect against As2O3-induced cardiotoxicity in vivo. Methods: Thirty-two male Wistar rats (150 to 200 g) were divided to 4 treatment groups: control (0.2 mL of saline, ip), As2O3 (5 mg/kg, ip), As2O3 plus MONT, and MONT (20 mg/kg, po). All drugs were administered daily for 10 days and pretreatment with MONT was performed 1 hour prior to As2O3 administration. Cardiotoxicity was estimated by electrocardiological, biochemical, and histopathological evaluations. Results: The results indicated that the combination treatment of montelukast and As2O3 markedly (P < 0.05) inhibited As2O3-induced lipid peroxidation and attenuated QT interval (QT) prolongation and histopathological alterations. Pretreatment with montelukast also suppressed increased troponin I and creatinine kinase-muscle brain (CK-MB) isoenzyme levels in response to As2O3 (P < 0.01). Conclusions: In conclusion, the current results demonstrated that montelukast possesses beneficial cardio-protective properties against As2O3 toxicity. It was also proposed that these protective effects were mediated by antioxidant modifications of montelukast.