Dexmedetomidine attenuates lipopolysaccharide-induced liver oxidative stress and cell apoptosis in rats by increasing GSK-3β/MKP-1/Nrf2 pathway activity via the α2 adrenergic receptor

Sha, Jichen; Zhang, Huayun; Zhao, Yuan; Feng, Xiujing; Hu, Xueyuan; Wang, Chaoran; Song, Manyu; Fan, Honggang

doi:10.1016/j.taap.2018.12.017

Cited by 47 publications

(48 citation statements)

References 41 publications

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“…Via α2-adrenergic receptors, deX has demonstrated sedative, analgesic, anti-anxiety and diuresis effects (40,41). in addition, the anti-apoptosis effect of deX was inhibited by the α2-adrenoceptor antagonist aTi in liver ischemia-reperfusion injury and renal ischemia-reperfusion injury (10,18). The present study further demonstrated that the antioxidant and anti-inflammatory action of DEX in lung injury during IIR was also acting on the α2-adrenoceptor.…”

Section: Discussionsupporting

confidence: 69%

“…all experimental procedures of the present study were performed in compliance with the national institutes of Health Guide for the care and use of laboratory animals (15). adult male Sprague-dawley (Sd) rats (8)(9)(10)(11)(12) weeks old, 200-250 g) were provided by the animal experimental center of Fudan university. The animals were housed in a room with a 12 h light-dark cycle under controlled environmental conditions with a temperature of 22±1˚C and a relative humidity of 55±5%.…”

Section: Methodsmentioning

confidence: 99%

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Pretreatment with dexmedetomidine alleviates lung injury in a rat model of intestinal ischemia reperfusion

Chen

Bian

2020

Mol Med Report

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The aim of the present study was to investigate the antioxidant mechanisms of dexmedetomidine against lung injury during intestinal ischemia reperfusion (iir) in rats. The model of iir-induced acute lung injury was established by occluding the superior mesenteric artery (SMa) for 1 h and reperfusing for 2 h using Sprague-dawley rats. Pathological examination was used to assess the extent of the lung injury. oxidative stress was evaluated by measuring malondialdehyde, myeloperoxidase and superoxide dismutase in the lung and plasma. The proinflammatory cytokines tumor necrosis factor-α and interleukin-6 were determined via an enzyme-linked immunosorbent assay. The mrna and protein expression of nuclear factor-erythroid 2 related factor 2 (nrf2) and heme oxygenase 1 (Ho-1) were determined using a reverse transcription-quantitative polymerase chain reaction and western blotting. Pretreatment with dexmedetomidine significantly inhibited the oxidative stress response and proinflammatory factor release caused by IIR compared with the normal saline group (Mda and Sod in lung and plasma, P<0.05; MPo, il-1β and TnF-α in lung and plasma, P<0.05). dexmedetomidine improved pulmonary pathological changes in iir rats compared with the normal saline group. investigations into the molecular mechanism revealed that dexmedetomidine increased the expression levels of nrf2 and Ho-1 via activating α2 adrenergic receptors compared with the normal saline group. The antagonism of α2 adrenergic receptors may reverse the protective effect of dexmedetomidine on lung injury during iir, including decreasing the expression levels of nrf2 and Ho-1, elevating the oxidative stress response and increasing the proinflammatory factor release. in conclusion, pretreatment with dexmedetomidine demonstrated protective effects against lung injury during iir via α2 adrenergic receptors. The nrf2/Ho-1 signaling pathway may serve a function in the protective effect of dexmedetomidine.

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Section: Discussionsupporting

confidence: 69%

Section: Methodsmentioning

confidence: 99%

Pretreatment with dexmedetomidine alleviates lung injury in a rat model of intestinal ischemia reperfusion

Chen

Bian

2020

Mol Med Report

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“…As the most promising area of research the use of α2-AM cytoprotectors and antioxidants should be considered. The effects of the protective effect on alveolocytes [47], cardiomyocytes [48,49], hepatocytes [50] are described in details in literature. To date, the mechanisms of such action are at the initial stage of their study.…”

Section: The Analysis Of Trends and Directions Of Research Of α2-am-amentioning

confidence: 99%

“…To date, the mechanisms of such action are at the initial stage of their study. It is known about the reduction of lipid peroxidation products, the production of peroxynitrile radicals [51], the stimulation of the activity of endogenous glutathione and superoxide dismutase [52]. A significant role in this case is given to stabilization of the inner mitochondrial membranes [53,54].…”

Section: The Analysis Of Trends and Directions Of Research Of α2-am-amentioning

confidence: 99%

Tendencies and perspectives of central alpha2-adrenomimetic application in medicobiological research

et al. 2019

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The pharmacodynamic effects of the administration of 2-adrenergic agonists both in a monovariant and in combination with drugs of other pharmacological groups are considered. Based on analysis of safety nonclinical studies the characteristics of main physiological effects of 2-adrenergic receptors as well as physiological effects of 2-agonists on various organs and systems are presented. For the determination of tendencies and directions in research of central 2-AM (dexmedetomidine) the analysis of bibliographical data, accumulated and extracted from Medline database with 5 year time-filter (VOSviewer, 1.6.11 version) has been carried out. For the further research of central 2-adrenomimetics and their application in clinical practice the following perspective directions have been determined: the study of effects and mechanisms of cytoprotectant and antioxidant action, the study of the use of drugs in a monovariant and in combinations for the development of analgesic drugs, anesthesia and development of combined formulations with a delayed release of antagonists designed to mitigate side effects.

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“…Xuanfei and colleagues demonstrated protection against the progression of hepatic fibrosis by the α2-AR blocker idazoxan [8]. In contrast, a recent in vivo study by Sha and colleagues showed that the antiapoptotic and antioxidative effects of the α2-AR agonist dexmedetomidine in the livers of rats with lipopolysaccharide-induced oxidative stress are reversed by the α2-AR antagonist atipamezole [14].…”

Section: Introductionmentioning

confidence: 99%

α2-Adrenergic Receptor in Liver Fibrosis: Implications for the Adrenoblocker Mesedin

Schwinghammer

Melkonyan

Hunanyan

et al. 2020

Cells

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The noradrenergic system is proposed to play a prominent role in the pathogenesis of liver fibrosis. While α1- and β-adrenergic receptors (ARs) are suggested to be involved in a multitude of profibrogenic actions, little is known about α2-AR-mediated effects and their expression pattern during liver fibrosis and cirrhosis. We explored the expression of α2-AR in two models of experimental liver fibrosis. We further evaluated the capacity of the α2-AR blocker mesedin to deactivate hepatic stellate cells (HSCs) and to increase the permeability of human liver sinusoidal endothelial cells (hLSECs). The mRNA of α2a-, α2b-, and α2c-AR subtypes was uniformly upregulated in carbon tetrachloride-treated mice vs the controls, while in bile duct-ligated mice, only α2b-AR increased in response to liver injury. In murine HSCs, mesedin led to a decrease in α-smooth muscle actin, transforming growth factor-β and α2a-AR expression, which was indicated by RT-qPCR, immunocytochemistry, and Western blot analyses. In a hLSEC line, an increased expression of endothelial nitric oxide synthase was detected along with downregulated transforming growth factor-β. In conclusion, we suggest that the α2-AR blockade alleviates the activation of HSCs and may increase the permeability of liver sinusoids during liver injury.

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Dexmedetomidine attenuates lipopolysaccharide-induced liver oxidative stress and cell apoptosis in rats by increasing GSK-3β/MKP-1/Nrf2 pathway activity via the α2 adrenergic receptor

Cited by 47 publications

References 41 publications

Pretreatment with dexmedetomidine alleviates lung injury in a rat model of intestinal ischemia reperfusion

Pretreatment with dexmedetomidine alleviates lung injury in a rat model of intestinal ischemia reperfusion

Tendencies and perspectives of central alpha2-adrenomimetic application in medicobiological research

α2-Adrenergic Receptor in Liver Fibrosis: Implications for the Adrenoblocker Mesedin

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