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Renoprotective effects of dexmedetomidine against ischemia-reperfusion injury in streptozotocin-induced diabetic rats.

 Seung Hyun Kim  ;  Ji Hae Jun  ;  Ju Eun Oh  ;  Eun-Jung Shin  ;  Young Jun Oh  ;  Yong Seon Choi 
 PLOS ONE, Vol.13(8) : e0198307, 2018 
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BACKGROUND: Diabetic patients are susceptible to renal ischemia-reperfusion injury, which leads to perioperative complications. Activation of NOD-like receptor protein 3 (NLRP3) inflammasome participates in the development of diabetes, and contributes to renal ischemia-reperfusion injury. Dexmedetomidine (DEX), 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 DEX treatment in diabetic rats. METHODS: Male Sprague-Dawley rats (n = 12 per group) were randomly divided into normal-sham, diabetes-sham, diabetes-ischemia-reperfusion-control, diabetes-ischemia-reperfusion-DEX-pre-treatment, and diabetes-ischemia-reperfusion-DEX-post-treatment groups. Renal ischemia-reperfusion injury was induced in diabetic rats by occlusion of both renal arteries for 45 min, followed by reperfusion for 24 h. DEX (10 μg/kg) was administered intraperitoneally 1 h before ischemia (pre-treatment) or upon reperfusion (post-treatment). After reperfusion, renal tissue was biochemically and histopathologically evaluated. RESULTS: DEX treatment attenuated ischemia reperfusion-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 DEX treatment. Furthermore, post-reperfusion treatment with DEX was significantly more effective than pre-treatment in modulating NLRP3 inflammasome, AKT and ERK signaling, and oxidative stress. CONCLUSIONS: This study shows that the protective effects of DEX in renal ischemia-reperfusion injury are preserved in diabetic conditions and may potentially provide a basis for the use of DEX in clinical treatment of renal ischemia-reperfusion injury.
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1. College of Medicine (의과대학) > Dept. of Anesthesiology and Pain Medicine (마취통증의학교실) > 1. Journal Papers
Yonsei Authors
Kim, Seung Hyun(김승현) ORCID logo https://orcid.org/0000-0003-2127-6324
Oh, Young Jun(오영준) ORCID logo https://orcid.org/0000-0002-6258-5695
Jun, Ji Hae(전지혜) ORCID logo https://orcid.org/0000-0002-8080-0715
Choi, Yong Seon(최용선) ORCID logo https://orcid.org/0000-0002-5348-864X
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