the evaluation of the ameliorative effect of montelukast against arsenic trioxide-induced cardiotoxicity in rats

Background: arsenic trioxide (as 2o3 ) 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 as2 o3 -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), as2 o3 (5 mg/kg, ip), as2 o3 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 as2 o3 administration. cardiotoxicity was estimated by electrocardiological, biochemical, and histopathological evaluations. results: the results indicated that the combination treatment of montelukast and as2 o3 markedly (p < 0.05) inhibited as2 o3 - 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 as2 o3 (p < 0.01). conclusions: in conclusion, the current results demonstrated that montelukast possesses beneficial cardio-protective properties against as2 o3 toxicity. it was also proposed that these protective effects were mediated by antioxidant modifications of montelukast.