scholarly journals Renoprotective effects Of Dexmedetomidine against ischemia-reperfusion injury in streptozotocin-induced diabetic rats

2018 ◽  
Author(s):  
Seung Hyun Kim ◽  
Ji Hae Jun ◽  
Ju Eun Oh ◽  
Eun-Jung Shin ◽  
Young Jun Oh ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Diabetic Rats ◽  
Post Treatment ◽  
Renal Ischemia ◽  
Erk Signaling ◽  
Renal Ischemia Reperfusion Injury ◽  
Pre Treatment

AbstractBackgroundDiabetic patients are susceptible to renal ischemia-reperfusion injury, which leads to perioperative complications. Nucleotide binding and oligomerization domain (NOD)-like receptor 3 inflammasome participates in the development of diabetes, and contributes to renal ischemia-reperfusion injury. Dexmedetomidine, a highly selective α2-adrenoreceptor agonist, shows renoprotective effects against ischemia-reperfusion injury. We aimed to elucidate the effects, underlying mechanisms, and optimal timing of dexmedetomidine treatment in diabetic rats.MethodsMale Sprague-Dawley rats (60 animals, weighing 250-300 g) were randomly divided into normal-sham, diabetes-sham, diabetes-ischemia-reperfusion-control, diabetes-ischemia-reperfusion-dexmedetomidine-pre-treatment, and diabetes-ischemia-reperfusion-dexmedetomidine-post-treatment groups. Renal ischemia-reperfusion injury was induced in diabetic rats by occlusion of both renal arteries for 45 minutes followed by reperfusion for 24 hours. Dexmedetomidine (10 μg/kg) was administered intraperitoneally 1 hour before ischemia (pre-treatment) or upon reperfusion (post-treatment). After reperfusion, renal tissue was biochemically and histopathologically evaluated.ResultsDexmedetomidine treatment attenuated IR-induced increase in NLRP3, caspase-1, IL-1β, phospho-AKT, and phospho-ERK signaling. Moreover, oxidative stress injury, inflammatory reactions, apoptosis, and renal tubular damage were favorably modulated by dexmedetomidine treatment. Furthermore, post-reperfusion treatment with dexmedetomidine was significantly more effective than pre-treatment in modulating inflammasome, AKT and ERK signaling, and oxidative stress.ConclusionsThis study shows that protective effects of dexmedetomidine in renal ischemia-reperfusion injury are preserved in diabetic conditions and may potentially provide a basis for the use of dexmedetomidine in clinical treatment of renal ischemia-reperfusion injury.

Hydrogen Sulfide Reduces Renal Ischemia-Reperfusion Injury by Enhancing Autophagy and Reducing Oxidative Stress

2021 ◽  
Author(s):  
Hui Li ◽  
Shuaiwei Wang ◽  
Shuangshuang An ◽  
Biao Gao ◽  
Tieshan Teng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Sulfide ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Renal Ischemia ◽  
Beclin 1 ◽  
Dependent Manner ◽  
Protein Levels ◽  
Renal Ischemia Reperfusion Injury

Abstract Background Renal ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury. Hydrogen sulfide (H2S) exerts a protective effect in renal IRI. The present study was carried out to investigate the effects of exogenous H2S on renal IRI by regulating autophagy in mice. Methods Mice were randomly assigned to control, IRI, and NaHS (28, 56 and 100 µmol/kg) groups. Renal IRI was induced by clamping the bilateral renal pedicles for with non-traumatic arterial clamp for 45 min and then reperfused for 24 h. Mice were administered intraperitoneally with NaHS 20 min prior to renal ischemia. Sham group mice underwent the same procedures without clamping. Serum and kidney tissues were harvested 24 h after reperfusion for functional, histological, oxidative stress, and autophagic determination. Results Compared with the control group, the concentrations of serum creatinine (Scr), blood urea nitrogen (BUN), and malondialdehyde (MDA), the protein levels of LC3II/I, Beclin-1, and P62, as well as the number of autophagosomes were significantly increased, but the activity of superoxide dismutase (SOD) was decreased after renal IRI. NaHS pretreatment dramatically attenuated renal IRI-induced renal dysfunction, histological changes, MDA concentration, and p62 expression in a dose-dependent manner. However, NaHS increased the SOD activity and the protein levels of LC3II/I and Beclin-1. Conclusions These results indicate that exogenous H2S protects the kidney from IRI through enhancement of autophagy and reduction of oxidative stress. Novel H2S donors could be developed in the treatment of renal IRI.

Sign in / Sign up

Export Citation Format

Share Document