Beneficial effects of bardoxolone methyl, an Nrf2 activator, on crush-related acute kidney injury in rats.
Acute kidney injury
Bardoxolone methyl
Crush syndrome
Nrf2
Journal
European journal of trauma and emergency surgery : official publication of the European Trauma Society
ISSN: 1863-9941
Titre abrégé: Eur J Trauma Emerg Surg
Pays: Germany
ID NLM: 101313350
Informations de publication
Date de publication:
Feb 2021
Feb 2021
Historique:
received:
04
03
2019
accepted:
21
08
2019
pubmed:
1
9
2019
medline:
6
7
2021
entrez:
1
9
2019
Statut:
ppublish
Résumé
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. 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. 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. 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.
Identifiants
pubmed: 31471671
doi: 10.1007/s00068-019-01216-z
pii: 10.1007/s00068-019-01216-z
doi:
Substances chimiques
Biomarkers
0
Oleanolic Acid
6SMK8R7TGJ
bardoxolone methyl
CEG1Q6OGU1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
241-250Subventions
Organisme : Dumlupınar University Scientific Research Projects Unit, Kütahya, Turkey
ID : 2016-16
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