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Beneficial effects of bardoxolone methyl, an Nrf2 activator, on crush-related acute kidney injury in rats

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Abstract

Purpose

The purpose of this study was to investigate the effects of bardoxolone methyl (BM), a nuclear factor erythroid 2-related factor 2 (Nrf2) activator, on acute kidney injury in a rat model of crush syndrome model.

Methods

Sixty-four rats were separated equally into eight groups, sham (sterile saline ip), crush, crush + vehicle (DMSO ip), and crush + BM (10 mg/kg ip) (n = 8). All groups were also divided as 3 and 24 h after decompression. Crush injury was induced by 6 h of direct compression to both hind limbs of the rats with blocks weighing 3.6 kg on each side, followed by 3 and 24 h of decompression. Kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), tumor necrotizing factor-α (TNF-α), transforming growth factor-β1 (TGF-β1) concentrations, tissue total oxidant status (TOS) and total antioxidant status (TAS) were measured in the kidneys. Serum creatine kinase (CK), blood urea nitrogen (BUN) and creatinine concentrations were also measured. Glomerular and tubular structures were examined histopathologically. Bcl-2 was measured using immunohistochemistry. Apoptosis was assessed using the TUNEL method.

Results

BM treatment reduced KIM-1, NGAL, TNF-α, TGF-β1, TOS concentrations, and increased TAS concentrations in the kidneys 3 and 24 h after decompression. Serum CK, BUN and creatinine concentrations were also reduced with BM. BM treatment decreased apoptosis in crush-related AKI. The Nrf2 activator BM reversed the crush-induced changes in the experimental rats.

Conclusion

BM treatment prevented the progression of crush-related AKI in rats possibly through its cytoprotective effects of being an antioxidant, anti-inflammatory and anti-apoptotic agent.

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Acknowledgements

This research was supported by Dumlupınar University Scientific Research Projects Unit, Kütahya, Turkey (Project no. 2016-16).

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Authors and Affiliations

  1. Department of Emergency Medicine, Faculty of Medicine, Kütahya Health Sciences University, Evliya Çelebi Yerleşkesi, 43000, Kutahya, Turkey

    Emine Kadıoğlu

  2. Department of Pharmacology, Faculty of Medicine, Kütahya Health Sciences University, Evliya Çelebi Yerleşkesi, 43000, Kutahya, Turkey

    Yasemin Tekşen

  3. Department of Pathology, Faculty of Medicine, Uşak University, Bir Eylül Kampüsü, 64000, Uşak, Turkey

    Cengiz Koçak

  4. Department of Biochemistry, Faculty of Medicine, Kütahya Health Sciences University, Evliya Çelebi Yerleşkesi, 43000, Kutahya, Turkey

    Fatma Emel Koçak

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  1. Emine Kadıoğlu
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Contributions

Study design: EK and YT. Animal studies and ELISA measurements: FEK and YT. Histopathologic examinations: CK. Biochemical measurement and interpretation: FEK. Manuscript writing and preparation of figures: YT and EK.

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Correspondence to Yasemin Tekşen.

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The authors declare that there are no conflicts of interest.

Ethical approval

The experimental protocol was approved by the animal ethical committee of Dumlupınar University (Approval no. 2015.11.02).

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Kadıoğlu, E., Tekşen, Y., Koçak, C. et al. Beneficial effects of bardoxolone methyl, an Nrf2 activator, on crush-related acute kidney injury in rats. Eur J Trauma Emerg Surg 47, 241–250 (2021). https://doi.org/10.1007/s00068-019-01216-z

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  • DOI: https://doi.org/10.1007/s00068-019-01216-z

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