Abstract
BackgroundKidney ischemia–reperfusion injury is a common pathophysiological phenomenon in the clinic. A large number of studies have found that the tyrosine protein kinase/signal transducer and activator of transcription (JAK/STAT) pathway is involved in the development of a variety of kidney diseases and renal protection associated with multiple drugs. Edaravone (EDA) is an effective free radical scavenger that has been used clinically for the treatment of postischemic neuronal injury. This study aimed to identify whether EDA improved kidney function in rats with ischemia–reperfusion injury by regulating the JAK/STAT pathway and clarify the underlying mechanism.MethodsHistomorphological analysis was used to assess pathological kidney injury, and mitochondrial damage was observed by transmission electron microscopy. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining was performed to detect tubular epithelial cell apoptosis. The expression of JAK2, P-JAK2, STAT3, P-STAT3, STAT1, P-STAT1, BAX and Bcl-2 was assessed by western blotting. Mitochondrial function in the kidney was assessed by mitochondrial membrane potential (ΔΨm) measurement.ResultsThe results showed that EDA inhibited the expression of p-JAK2, p-STAT3 and p-STAT1, accompanied by downregulation of the expression of Bax and caspase-3, and significantly ameliorated kidney damage caused by ischemia–reperfusion injury (IRI). Furthermore, the JC-1 dye assay showed that edaravone attenuated ischemia–reperfusion-induced loss of kidney ΔΨm.ConclusionOur findings indicate that EDA protects against kidney damage caused by ischemia–reperfusion through JAK/STAT signaling, inhibiting apoptosis and improving mitochondrial injury.
Highlights
Kidney ischemia–reperfusion injury is a common pathophysiological phenomenon in the clinic
Studies have shown that activation of the JAK/STAT signaling pathway contributes to the development of acute kidney injury [38, 39]; we used the JAK2-specific antagonist AG490 as a positive control treatment of kidney injury
The results indicated that Ischemia–reperfusion injury (IRI) increased MPO and CD68 levels in IRI kidney tissue (p < 0.001, Additional file 1: Figure S1), but after EDA and AG490 treatment, MPO and CD68 levels were reduced in IRI kidney tissue (p < 0.001, Additional file 1: Figure S1)
Summary
Kidney ischemia–reperfusion injury is a common pathophysiological phenomenon in the clinic. A large number of studies have found that the tyrosine protein kinase/signal transducer and activator of transcription (JAK/STAT) pathway is involved in the development of a variety of kidney diseases and renal protection associated with multiple drugs. Edaravone (EDA) is an effective free radical scavenger that has been used clinically for the treatment of postischemic neuronal injury. Increased ROS causes cell apoptosis in organs with ischemia–reperfusion injury, including the kidney [4]. Many studies have shown that EDA has protective effects against IRI of organs, such as reducing multiple erosions and bleeding injury in the small intestine induced by clamping the superior mesenteric artery for 30 min. EDA was administered into the femoral artery after reperfusion for 30 min, reducing malondialdehyde levels and preventing lipid peroxidation-mediated ischemia–reperfusion injury of the bladder. EDA reduced myeloperoxidase and malondialdehyde levels, indicating that EDA reduces oxidative stress and prevents testicular damage induced by ischemia–reperfusion [12,13,14,15]
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