Department of Pharmacology, Faculty of Medicine, Assiut University, Assiut, Egypt.
Department of Pathology, Faculty of Veterinary Medicine, Assiut University, Assiut, Egypt.
Drug Dev Res. 2019 Nov;80(7):1000-1009. doi: 10.1002/ddr.21581. Epub 2019 Aug 6.
Montelukast (MNK) has prominent anti-inflammatory and antioxidant activities. It can protect the liver in different hepatotoxic models in animals. Simvastatin (SMV) is one of commonly used lipid lowering drugs for treatment of dyslipidemia in order to reduce cardiovascular disease. It has severe side effects such as myopathy and hepatotoxicity. The aim of the present study is to investigate the possible effect of MNK on SMV-induced myopathy and hepatotoxicity. Four groups of male rats: control group which received saline via stomach tube, MNK treated group (received 10 mg/kg/day MNK via stomach tube), SMV treated group (received 30 mg/kg/day SMV via stomach tube), and MNK + SMV (combination) group which received both MNK and SMV. All animals were treated for 14 days before obtaining blood and tissue samples. SMV has both hepatotoxic effects and myopathy. SMV caused a significant increase in myoglobin, creatinine kinase, ALT, AST, ALP, and bilirubin but, it decreased total proteins, globulin and albumin levels. Co-treatment of SMV and MNK increased the antioxidant activity significantly. MNK modifies partially the myopathic changes and hepatotoxic effect of SMV. Co-administration of MNK and SMV decreased their toxic potentials on the liver, skeletal muscles, and kidney. They have antioxidant activities when given together that produce muscle and hepatic protective effects.
孟鲁司特（MNK）具有显著的抗炎和抗氧化活性。它可以在不同的动物肝毒性模型中保护肝脏。辛伐他汀（SMV）是一种常用的降脂药物，用于治疗血脂异常，以降低心血管疾病的风险。它有严重的副作用，如肌病和肝毒性。本研究旨在探讨 MNK 对 SMV 诱导的肌病和肝毒性的可能影响。四组雄性大鼠：对照组经胃管给予生理盐水，MNK 治疗组（经胃管给予 10mg/kg/天 MNK），SMV 治疗组（经胃管给予 30mg/kg/天 SMV），MNK+SMV（联合）组给予 MNK 和 SMV。所有动物在获得血液和组织样本前均接受治疗 14 天。SMV 既有肝毒性又有肌病。SMV 导致肌红蛋白、肌酸激酶、ALT、AST、ALP 和胆红素显著增加，但总蛋白、球蛋白和白蛋白水平降低。SMV 和 MNK 的联合治疗显著增加了抗氧化活性。MNK 部分改变了 SMV 的肌病变化和肝毒性作用。MNK 和 SMV 的联合给药降低了它们对肝脏、骨骼肌和肾脏的毒性潜力。它们具有抗氧化活性，同时具有肌肉和肝脏保护作用。
