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Eur J Trauma Emerg Surg. 2019 Aug 30. doi: 10.1007/s00068-019-01216-z. [Epub ahead of print]

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

Author information

1
Department of Emergency Medicine, Faculty of Medicine, Kütahya Health Sciences University, Evliya Çelebi Yerleşkesi, 43000, Kutahya, Turkey.
2
Department of Pharmacology, Faculty of Medicine, Kütahya Health Sciences University, Evliya Çelebi Yerleşkesi, 43000, Kutahya, Turkey. yasemin.teksen@ksbu.edu.tr.
3
Department of Pathology, Faculty of Medicine, Uşak University, Bir Eylül Kampüsü, 64000, Uşak, Turkey.
4
Department of Biochemistry, Faculty of Medicine, Kütahya Health Sciences University, Evliya Çelebi Yerleşkesi, 43000, Kutahya, Turkey.

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.

KEYWORDS:

Acute kidney injury; Bardoxolone methyl; Crush syndrome; Nrf2

PMID:
31471671
DOI:
10.1007/s00068-019-01216-z

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