Renoprotective effects of montelukast, a cysteinyl leukotriene receptor antagonist, against methotrexate-induced kidney damage in rats

摘要: Methotrexate (MTX) is a cytotoxic chemotherapeutic agent used for treatment of several cancers. Nephrotoxicity, an adverse side effect high-dose MTX, attributed to abnormal production reactive oxygen species (ROS), inflammatory mediators, and neutrophil infiltration. Montelukast (MON) cysteinyl leukotriene receptor antagonist. Recently, it has gained considerable interest as ROS scavenger modulator. In this study, we investigated the MON against MTX-induced nephrotoxicity. Rats were divided into four groups: control group, group (10 mg/kg, orally), MTX (20 i.p., single injection), + (MON was administered 5 days before after administration). At end experiment, serum collected analysis blood urea nitrogen (BUN) creatinine. Glutathione (GSH), lipid peroxides (malondialdehyde), tumor necrosis factor alpha (TNF-α) levels, superoxide dismutase, myeloperoxidase activities, nuclear kappa beta (NF-κB) protein expression determined in renal tissues. addition, kidney tissues examined histopathologically immunohistochemically NF-κB. administration produced acute damage indicated from severe elevation BUN The role oxidative stress mechanisms nephrotoxicity evidenced unbalance tissue parameters, increased TNF-α NF-κB On other hand, significantly reduced toxic effects indicted normalization kidney-specific stress, mediators. This data further supported by histopathological studies. Thus, co-administration may be promising alleviating systemic MTX.