Gad Amany M, El-Raouf Ola M Abd, El-Sayeh Bahia M, Fawzy Hala M, Abdallah Dalaal M
Department of Pharmacology, National Organization for Drug Control and Research (NODCAR), Giza, Egypt.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
J Biochem Mol Toxicol. 2017 Dec;31(12). doi: 10.1002/jbt.21979. Epub 2017 Sep 13.
Renal toxicity is one of the most severe complications that can occur with cisplatin (CIS) administration in cancer patients. Montelukast (ML) renoprotective outcome contrary to CIS-drawn nephrotoxicity remains obscure. Therefore, adult male Sprague-Dawley rats were orally given ML (10 and 20 mg/kg/day) 5 days before and after single CIS (5 mg/kg; i.p.) treatment. ML returned blood urea nitrogen, as well as serum creatinine and gamma glutamyl transferase that were elevated by CIS to normal level. The improved kidney function tests corroborated the attenuation of CIS renal injury at the microscopical level. It also reduced serum/renal nitric oxide and renal hemeoxygenase-1. Meanwhile, ML hindered the raised levels of serum endothelin-1, serum and renal tumor necrosis factor-α, and monocyte chemoattractant protein-1. These effects were associated by deceased caspase-3 expression in kidney after ML treatment. In conclusion, ML guards against CIS-induced nephrotoxicity via anti-inflammatory and antiapoptotic properties.
肾毒性是癌症患者使用顺铂(CIS)时可能发生的最严重并发症之一。孟鲁司特(ML)对CIS所致肾毒性的肾脏保护作用仍不清楚。因此,在成年雄性Sprague-Dawley大鼠单次腹腔注射CIS(5mg/kg)治疗前后5天,分别口服给予ML(10和20mg/kg/天)。ML使CIS升高的血尿素氮、血清肌酐和γ-谷氨酰转移酶恢复到正常水平。肾功能测试的改善证实了CIS肾损伤在微观水平上的减轻。它还降低了血清/肾脏一氧化氮和肾脏血红素加氧酶-1。同时,ML抑制了血清内皮素-1、血清和肾脏肿瘤坏死因子-α以及单核细胞趋化蛋白-1水平的升高。这些作用与ML治疗后肾脏中半胱天冬酶-3表达降低有关。总之,ML通过抗炎和抗凋亡特性预防CIS诱导的肾毒性。