Preventitative effect of montelukast in the radiocontrast induced nephropathy in RATS VIA NF-KB, NOX4 AND P22 phox expression

In pathophysiology of contrast-induced nephropathy, reactive oxygen species generation, inflammation and apoptosis are observed. NOX4 is mostly expressed in the kidney, co-localized with p22phox and main regulatory enzyme for ROS generation. Montelukast has antioxidant, anti-inflammatory and anti-apoptotic properties. Therefore this study investigated the effect of montelukast pre-treatment for preventing contrast-induced nephropathy in rats, via NF-κB, NOX4 and p22 phox expressions. Nephropathy model was initiated by administration of 10 mg/kg indomethacin, 10 mg/kg NG-Nitro-L-arginine methyl ester and 3 g I/kg iohexol at 15-minute intervals after 16h of water deprivation on 6th day. Rats were sacrificed on the 8th day under thiopental sodium anesthesia. All enjections are performed intraperitoneally. After the initiation of nephropathy model; serum KIM-1 levels, TNF-α, NF-κB, NOX4, p22phox and KIM-1 mRNA expressions, tissue ROS levels, tubular injury score and apoptosis increased compared to control group. Administration of 10 mg/kg montelukast, decreased serum KIM-1 levels, TNF-α, NF-κB, NOX4, p22phox and KIM-1 mRNA expressions, tissue ROS levels and NF-κB p65 protein expression. These results suggest that montelukast pre-treatment has a protective effect in contrast-induced nephropathy. It is possible that montelukast could be used as a useful agent for preventing contrast-induced nephropathy. Further studies needed for evaluating the efficacy of montelukast pretreatment in contrast-induced nephropathy.