Protective effects of cerium oxide on ibuprofen-induced renal injury in rats with ureteral obstruction

doi:10.5527/wjn.v15.i1.114142

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World Journal of Nephrology

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Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Nephrol. Mar 25, 2026; 15(1): 114142
Published online Mar 25, 2026. doi: 10.5527/wjn.v15.i1.114142

Protective effects of cerium oxide on ibuprofen-induced renal injury in rats with ureteral obstruction

Salih Toruk, Avni Babacan, Mustafa Arslan, Volkan Şıvgın, Şaban Cem Sezen, Hakan Boyunağa

Salih Toruk, Avni Babacan, Mustafa Arslan, Volkan Şıvgın, Department of Anesthesiology and Reanimation, Gazi University Faculty of Medicine, Ankara 06560, Türkiye

Şaban Cem Sezen, Department of Histology and Embryology, Faculty of Medicine, Kırıkkale University, Kırıkkale 71100, Türkiye

Hakan Boyunağa, Department of Medical Biochemistry, Faculty of Medicine, Kırıkkale University, Kırıkkale 71100, Türkiye

Co-corresponding authors: Salih Toruk and Mustafa Arslan.

Author contributions: Toruk S drafted the manuscript; Toruk S and Arslan M designed the research study, analyzed and interpreted the data, and they contributed equally to this manuscript as co-corresponding authors; Toruk S, Babacan A, and Şıvgın V performed the animal experiments; Sezen ŞC and Boyunağa H conducted biochemical and histopathological analyses. All authors critically revised the manuscript, approved the final version, and agreed to be accountable for all aspects of the work.

Institutional animal care and use committee statement: This experimental study was approved by the Animal Experiments Local Ethics Committee of Gazi University (approval No: G.Ü.ET-19.049) and conducted at the Gazi University Laboratory Animal Research Center.

Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.

ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.

Data sharing statement: The datasets generated and analyzed during the current study are available from the corresponding author upon reasonable request.

Corresponding author: Salih Toruk, MD, Department of Anesthesiology and Reanimation, Gazi University Faculty of Medicine, No. 47 Emniyet Mh. Mevlana Blv., Ankara 06560, Türkiye. salihtoruk@gmail.com

Received: September 12, 2025
Revised: October 27, 2025
Accepted: January 8, 2026
Published online: March 25, 2026
Processing time: 183 Days and 8.5 Hours

Abstract

BACKGROUND

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for pain management, but they can cause nephrotoxicity, particularly in patients with existing renal impairment. Cerium oxide (CeO₂), an antioxidant nanoparticle, may provide protection against renal damage caused by NSAIDs.

AIM

To assess the protective effects of CeO₂ against ibuprofen-induced renal injury in a rat model of unilateral ureteral obstruction (UUO).

METHODS

Thirty male Wistar albino rats, weighing between 300 g and 425 g, were randomly divided into five groups (n = 6 each): Control (sham), UUO only, UUO + ibuprofen, UUO + ibuprofen + CeO₂, and UUO + CeO₂. UUO was surgically induced in all groups except the control group. Treatments were administered for a duration of 21 days. Serum levels of blood urea nitrogen, creatinine, malondialdehyde, and nitric oxide were measured. In addition, histopathological analysis was performed on both kidneys to assess parameters such as glomerular vacuolization (GV), tubular dilation, vascular hypertrophy, tubular necrosis, Bowman’s space dilation, hyaline casts, lymphocyte infiltration, and tubular desquamation.

RESULTS

In the right (non-obstructed) kidneys, the UUO + CeO₂ group exhibited significantly lower levels of GV, tubular hyaline casts, and tubular desquamation compared to the UUO + ibuprofen group (P < 0.05). In the left (obstructed) kidneys, the CeO₂-treated group also exhibited significant reductions in GV, vascular hypertrophy, and tubular hyaline casts (P < 0.05). Furthermore, malondialdehyde levels were markedly decreased in the CeO₂ groups, whereas nitric oxide levels were elevated in the ibuprofen group. Blood urea nitrogen and creatinine levels increased across all UUO groups, but no significant differences were observed between the treatment groups.

CONCLUSION

CeO₂ attenuates ibuprofen-induced renal injury in rats with UUO, likely through antioxidative mechanisms. These findings suggest that CeO₂ could serve as a potential nephroprotective adjunct during NSAID therapy in patients with obstructive renal conditions.

Keywords: Cerium oxide; Ibuprofen; Non-steroidal anti-inflammatory drugs; Ureteral obstruction; Oxidative stress; Renal injury

Core Tip: This experimental study explores the protective effects of cerium oxide (CeO₂), a powerful antioxidant nanoparticle, against renal injury induced by ibuprofen in rats with unilateral ureteral obstruction. Histopathological and biochemical analyses demonstrated that CeO₂ significantly reduced tubular degeneration, glomerular vacuolization, and oxidative stress markers in both the obstructed and contralateral kidneys. These results indicate that CeO₂ may function as a nephroprotective adjunct during non-steroidal anti-inflammatory drug therapy, potentially mitigating renal damage associated with obstructive uropathy.