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. 2025 Jul;57(7):2313-2325.
doi: 10.1007/s11255-025-04378-5. Epub 2025 Feb 21.

Preventative effect of montelukast in mild to moderate contrast-induced acute kidney injury in rats via NADPH oxidase 4, p22phox and nuclear factor kappa-B expressions

Oguzhan Simsek  1 , Elif Baris #  1   2 , Cemre Ural #  3 , Canet Incir  4 , Selma Aydemir  5 , Mukaddes Gumustekin  4 , Zahide Cavdar  3 , Osman Yilmaz  6 , Seda Ozbal  7 , Mualla Aylin Arici  8
Affiliations

Preventative effect of montelukast in mild to moderate contrast-induced acute kidney injury in rats via NADPH oxidase 4, p22phox and nuclear factor kappa-B expressions

Oguzhan Simsek et al. Int Urol Nephrol. 2025 Jul.

Abstract

Reactive oxygen species (ROS) generation, inflammation and apoptosis are observed in contrast-induced acute kidney injury (CI-AKI). NOX4, isoform of NADPH oxidase main regulatory enzyme for ROS generation, is mostly expressed in the kidney and co-localized with p22phox. It is investigated the effect of antioxidant, anti-inflammatory and anti-apoptotic montelukast pre-treatment on expression of NOX4, p22phox and NF-κB in preventing CI-AKI in rats in this study. Wistar male rats randomized into four groups: 1. Control (C), 2. CI-AKI (iohexol; 3 g iodine/kg), 3. Montelukast (10 mg/kg) (M), 4. M + CI-AKI. Rats sacrificed on the 7th day. Urine and serum creatinine and serum Kidney injury molecule-1 (KIM-1) levels measured. NF-κB, NOX-4, p22phox mRNA and protein expressions, TNF-α, KIM-1 mRNA expressions, ROS and caspase-3 evaluated from kidney tissue. Histological injury scored. ANOVA and Kruskal-Wallis tests were used for analysis parametric and nonparametric data, respectively. p < 0.05 considered statistically significant. Tubular injury score, KIM-1 and caspase-3 levels increased in CI-AKI group compared to C group (p < 0.05). TNF-α, NF-κB, NOX-4, p22phox, KIM-1 mRNA expressions and ROS levels increased in CI-AKI group compared to C group (p < 0.001 and p < 0.05). NF-κB, NOX-4, p22phox protein expressions increased in CI-AKI group compared to C group (p < 0.05) and decreased in the M + CI-AKI group compared to CI-AKI group (p < 0.01, p < 0.05, p < 0.05). TNF-α, NF-κB, NOX-4, p22phox, KIM-1 mRNA expressions and ROS levels decreased with montelukast pre-treatment (p < 0.001). One of the mechanism of increased ROS level in the CI-AKI model is related the increase the expression of NOX4 and p22phox and montelukast pre-treatment has a protective effect by decreasing NOX4 and p22phox mRNA and protein expressions.

Keywords: Contrast-induced nephropathy; Montelukast; NOX4; Oxidative stress; p22phox.

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Conflict of interest statement

Declarations. Conflict of interest: The authors declare no competing interests.

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