Gallic Acid, Renal Redox Balance and NRF2-Related Transcript-Level Modulation in a Rat Model of Contrast-Associated Acute Kidney Injury.
Akyürek Bayhan Nurhan, Gündüz Demet, Fatih Karakuyu Nasıf, Ilhan İlter, Yusuf Tepebaşi Muhammet, Berk Imeci Orhan, Sarman Emine, Savran Mehtap
Abstract
INTRODUCTION: Contrast-associated acute kidney injury (CA-AKI) is a clinically relevant complication of iodinated contrast exposure. This study investigated whether gallic acid (GA) attenuates diatrizoate (Urografin 76%; URO)-induced renal injury in rats and whether this effect is associated with nuclear factor erythroid 2-related factor 2 (NRF2)/Kelch-like ECH-associated protein 1 (Keap-1)/heme oxygenase-1 (HO-1) transcript-level changes. METHODS: Thirty-two female Wistar rats were randomized into Control, URO, URO+GA, and GA groups (n=8/group). GA was administered intraperitoneally at 100 mg/kg 15 min before URO. At 24 h, serum urea and creatinine, renal total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), histopathology, tumor necrosis factor-alpha (TNF-alpha) and caspase-3 immunohistochemistry, and NRF2/Keap-1/HO-1 mRNA expression were evaluated. RESULTS: URO significantly increased serum urea and creatinine and induced renal oxidative imbalance, as shown by increased TOS and OSI and reduced TAS. GA co-treatment significantly decreased TOS and OSI and partially restored TAS, whereas urea and creatinine showed only non-significant downward trends. Histopathologically, GA attenuated collagenous material accumulation, while other acute tubular injury parameters were not significantly improved. TNF-alpha and caspase-3 immunoreactivity remained weak/focal without significant intergroup differences. URO reduced NRF2, Keap-1, and HO-1 mRNA levels, whereas GA restored these transcripts toward control values. CONCLUSION: GA was associated with biochemical and transcript-level attenuation of acute diatrizoate-induced CA-AKI, mainly through improved renal redox balance and restoration of NRF2-related transcripts. However, functional renoprotection and NRF2 pathway activation were not definitively demonstrated.
Key Findings
- Diatrizoate (Urografin 76%) induced renal oxidative imbalance, increasing total oxidant status (TOS) and oxidative stress index (OSI), and reducing total antioxidant status (TAS).
- Gallic acid (GA) co-treatment significantly decreased TOS and OSI and partially restored TAS in a rat model of contrast-associated acute kidney injury (CA-AKI).
- GA restored NRF2, Keap-1, and HO-1 mRNA transcript levels toward control values, suggesting modulation of the NRF2-related antioxidant pathway.
Clinical Significance
Gallic acid may offer biochemical and transcript-level protection against contrast-induced acute kidney injury by improving renal redox balance and modulating NRF2-related antioxidant pathways, although definitive functional renoprotection was not established.
Citation
Akyürek Bayhan Nurhan, Gündüz Demet, Fatih Karakuyu Nasıfet al.. Gallic Acid, Renal Redox Balance and NRF2-Related Transcript-Level Modulation in a Rat Model of Contrast-Associated Acute Kidney Injury. European journal of pharmacology. 2026-Aug-21.