Molecular targets and mechanism of action of dexmedetomidine in treatment of ischemia/reperfusion injury (Review)

Abstract

Abstract. Dexmedetomidine (DEX), a highly specific α 2 -adrenergic agonist, which exhibits anaesthetic-sparing, analgesia and sympatholytic properties. DEX modulates gene expression, channel activation, transmitter release, inflammatory processes and apoptotic and necrotic cell death. It has also been demonstrated to have protective effects in a variety of animal models of ischemia/reperfusion (I/R) injury, including the intestine, myocardial, renal, lung, cerebral and liver. The broad spectrum of biological activities associated with DEX continues to expand, and its diverse effects suggest that it may offer a novel therapeutic approach for the treatment of human diseases with I/R involvement.

Dexmedetomidine protects the heart against ischemia-reperfusion injury by an endothelial eNOS/NO dependent mechanism

“…In this context, Dex has shown detrimental effects in the myocardium when used as a post-conditioning rather than a pre-conditioning agent [48]. This observation lead Cai et al to hypothesize that the protective effect of Dex depends on timing [10]. Our study may support this idea, since NO is known to be cardioprotective against IR injury [49,50].…”

“…The modulation of the sympathetic nervous system theoretically maintains the balance in the input/demand relationship of myocardial oxygen. Dex is known to be protective in multiple organs and types of ischemiareperfusion (IR) injury [10]. The mechanism by which it protects may be organspecific.…”

Honokiol protects against renal ischemia/reperfusion injury via the suppression of oxidative stress, iNOS, inflammation and STAT3 in rats

“…This is often accompanied by renal ischemia and reperfusion, which affect treatment outcomes (1,2). Therefore, reducing or avoiding IRI is one of the areas in renal protection, which has received significant attention.…”

Neuroprotection of dexmedetomidine against propofol-induced neuroapoptosis partly mediated by PI3K/Akt pathway in hippocampal neurons of fetal rat

“…Since the antagonist atipamezole of the α2-adrenoceptor only partly reversed the neuroprotective effects of dexmedetomidine on neurotoxicity in rats induced by isoflurane, there may be other mechanisms. Several pathways have been reportedly involved in the neuroprotection of dexmedetomidine (Cai et al, 2014;Duan et al, 2014;Liao et al, 2014;Xiong et al, 2014). Li et al (2014) found that dexmedetomidine pretreatment dose-dependently inhibited isofluraneinduced neuroapoptosis by preserving the PI3K/Akt pathway in the hippocampus in neonatal rats.…”