Dexmedetomidine Ameliorate CLP‐Induced Rat Intestinal Injury via Inhibition of Inflammation

Abstract

The aim was to verify that dexmedetomidine (DEX) can attenuate CLP-induced intestinal injury via inhibition of inflammation. Male Sprague-Dawley (SD) rats were randomly allocated into Sham group and the other three CLP model groups, in terms of different treatments: placebo, DEX, and yohimbine plus DEX (DEX + YOH) groups. Pathology examination was conducted with HE stain. To identify differences among groups, the levels of DAO, and D-lactate in serum were measured by spectrophotometry, and the levels of TNF-α, IL-1β, and IL-6 in serum and organ were measured by ELISA. The expressions of occludin and TLR4 in tissue were detected by Western blot. The survival rate of an additional group of animals within 7 d was recorded. In DEX group, mortality was lower, histology change was minor, DAO, and D-lactate levels were reduced, and occludin expression was increased; the expressions of TNF-α, IL-1β, IL-6, and TLR4 were also decreased in DEX group. These results indicated that acute intestinal injury induced by CLP was mitigated by DEX treatment. However, these effects of DEX were significantly attenuated by yohimbine in DEX + YOH group. Our study indicated the protective effects of DEX on CLP-induced injury, which may be associated with the inhibition of inflammation via modulating TLR4 pathway and can be blocked by yohimbine.

Dexmedetomidine reduces ventilator-induced lung injury (VILI) by inhibiting Toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB signaling pathway

“…As a widely used anesthetic adjuvant in clinical setting, dexmedetomidine has a high affinity for the α 2 -adrenoceptor and is approved for sedation in critically ill patients, due to its sedative effects without respiratory depression [6]. Many studies also showed the anti-inflammatory effect of dexmedetomidine by reducing the levels of inflammatory cytokines in some specific cases [7,23,24]. Based on previous research [9], we set the dose of dexmedetomidine at 1 µg/kg/hour which is the equivalent of the clinical dose in humans.…”

Dexmedetomidine-mediated neuroprotection against sevoflurane-induced neurotoxicity extends to several brain regions in neonatal rats

“…27 There is increasing evidence that DEX has organ protective properties in several injury models including ischaemiareperfusion, inflammation, and traumatic brain injury. [28][29][30][31][32] More recently, DEX has been shown to be protective against neurotoxicity induced by ketamine and isoflurane in a neonatal rat model. 33 34 Sevoflurane (SEVO) is the preferred and most frequently used volatile anaesthetic in paediatric anaesthesia.…”

Is Dexmedetomidine the Key for Reducing Acute Kidney Injury After Cardiac Surgery?

“…Dexmedetomidine also may provide anti-inflammatory benefits in response to surgical stress through cytokine inhibition and suppression of adrenoceptor-mediated vascular constriction in the renal structures. 7,8 These effects perhaps explain the Peng et al findings of reduced AKI with dexmedetomidine use, specifically in the preoperative and intraoperative settings, irrespective of postoperative use. With the temporal insult of cardiopulmonary bypass, early preservation of the renal vasculature may serve as a mechanism for prevention of phenotypic AKI in the post-bypass setting.…”

“…A similar hypothesis has been proposed for early prophylactic dexmedetomidine application in sepsis to protect against intestinal injury. 7,8 The Peng et al study is not without limitation. The 9 studies included in the analysis spanned nearly a decade, and therefore several different definitions were used to characterize AKI.…”