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


Simsek O., Baris E., Ural C., Incir C., Aydemir S., GÜMÜŞTEKİN M., ...Daha Fazla

INTERNATIONAL UROLOGY AND NEPHROLOGY, cilt.57, sa.7, ss.2313-2325, 2025 (SCI-Expanded, Scopus) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 57 Sayı: 7
  • Basım Tarihi: 2025
  • Doi Numarası: 10.1007/s11255-025-04378-5
  • Dergi Adı: INTERNATIONAL UROLOGY AND NEPHROLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, EMBASE, Gender Studies Database
  • Sayfa Sayıları: ss.2313-2325
  • Anahtar Kelimeler: Contrast-induced nephropathy, Montelukast, Oxidative stress, NOX4, p22phox
  • Dokuz Eylül Üniversitesi Adresli: Evet

Özet

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-kappa B 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-kappa B, NOX-4, p22phox mRNA and protein expressions, TNF-alpha, 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-alpha, NF-kappa B, 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-kappa B, 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-alpha, NF-kappa B, 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.