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Edaravone Ameliorates Renal Warm Ischemia-Reperfusion Injury by Downregulating Endoplasmic Reticulum Stress in a Rat Resuscitation Model

Authors Fu ZY, Wu ZJ, Zheng JH, Li N, Lu JY, Chen MH

Received 17 April 2019

Accepted for publication 5 December 2019

Published 15 January 2020 Volume 2020:14 Pages 175—183


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Yan Zhu

Zhao-Yin Fu, Zhi-Jiang Wu, Jun-Hui Zheng, Nuo Li, Jun-Yu Lu, Meng-Hua Chen

Department of Critical Care Medicine, Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530007, People’s Republic of China

Correspondence: Meng-Hua Chen
Department of Critical Care Medicine, Second Affiliated Hospital of Guangxi Medical University, 166 Daxuedong Road, Nanning, Guangxi 530007, People’s Republic of China
Tel +86 771 327 7186

Background: This study was conducted to explore whether the effect of edaravone (5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol3-one, EDR) can ameliorate renal warm ischemia-reperfusion injury (IRI) by modulating endoplasmic reticulum stress (ERS) and its downstream effector after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) in a rat model.
Methods: The rats (n=10) experienced anaesthesia and intubation followed by no CA inducement were defined as the Sham group. Transoesophageal alternating current stimulation was employed to establish 8 min of CA followed by conventional CPR for a resuscitation model. The rats with successful restoration of spontaneous circulation (ROSC) randomly received EDR (3 mg/kg, EDR group, n=10) or equal volume normal saline solution (the NS group, n=10). At 24 hr after ROSC, serum creatinine (SCR), blood urea nitrogen (BUN) levels, and cystatin-C (Cys-C) levels were determined and the protein level of glucose-regulated protein (GRP78), C/EBP homologous protein (CHOP), extracellular signal-regulated kinase (ERK), phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2), Bax/Bcl-2, and caspase-3 were detected by Western blot method.
Results: At 24 hrs after ROSC, SCR, BUN and Cys-C were obviously increased and the proteins expression, including GRP78, CHOP and p-ERK1/2, cleaved-caspase 3 Bax/Bcl-2 ratio, were significantly upregulated in the NS group compared with the Sham group (p< 0.05). The remarkable improvement of these adverse outcomes was observed in the EDR group (p< 0.05).
Conclusion: In conclusion, we found that EDR ameliorates renal warm IRI by downregulating ERS and its downstream effectors in a rat AKI model evoked by CA/CPR. These data may provide evidence for future therapeutic benefits of EDR against AKI induced by CA/CPR.

Keywords: renal warm ischemia-reperfusion injury, edaravone, endoplasmic reticulum stress, cardiac arrest, cardiopulmonary resuscitation

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