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bioRxiv · 10.1101/325894

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

Kim, S. H.·Jun, J. H.·Oh, J. E.·Shin, E.-J.·Oh, Y. J.·Choi, Y. S.
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Abstract

BackgroundDiabetic 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 2-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.\n\nMethodsMale 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 g/kg) was administered intraperitoneally 1 hour before ischemia (pre-treatment) or upon reperfusion (post-treatment). After reperfusion, renal tissue was biochemically and histopathologically evaluated.\n\nResultsDexmedetomidine treatment attenuated IR-induced increase in NLRP3, caspase-1, IL-1{beta}, 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.\n\nConclusionsThis 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.

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Kim, S. H., Jun, J. H., Oh, J. E., Shin, E.-J., Oh, Y. J., Choi, Y. S.. 2018-05-18. Renoprotective effects Of Dexmedetomidine against ischemia-reperfusion injury in streptozotocin-induced diabetic rats. https://doi.org/10.1101/325894

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