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

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.

Abstract licence: CC BY

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