Dexmedetomidine activates the PI3K/Akt pathway to inhibit hepatocyte apoptosis in rats with obstructive jaundice

Xie, Yaying; Guo, Chunyan; Liu, Ye; Shi, Luanyuan; Yu, Jianshe

doi:10.3892/etm.2019.8085

Cited by 4 publications

(3 citation statements)

References 28 publications

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“…LY294002 pretreatment abolished the protective effects of DEX on LPS-induced inflammatory cell infiltration, oxidative stress, and apoptosis in the lungs. Similar to our results, a previous study found that DEX significantly reduced lung injury in rats with obstructive jaundice through activation of the PI3K/Akt/HIF-1α signaling pathway [ 35 ]. DEX decreased the expression of IL-6 and TNF-α in obstructive jaundice rats [ 36 ].…”

Section: Discussionsupporting

confidence: 92%

Dexmedetomidine ameliorates lipopolysaccharide-induced acute lung injury by inhibiting the PI3K/Akt/FoxO1 signaling pathway

Cui

Zhang

2021

J Anesth

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Purpose Dexmedetomidine (DEX) has been associated with inflammation, oxidative stress, and apoptosis, but its effects on lipopolysaccharide (LPS)-induced lung injury remain uncertain. The present study explored the effects of DEX on LPS-induced lung injury and studied the possible molecular mechanisms by testing the effects of the phosphoinositide-3 kinase (PI3K) inhibitor LY294002 and BEZ235. Methods Seventy C57BL/6 mice were randomly divided into the control, LPS, LPS + DEX, LPS + LY294002, LPS + BEZ235, LPS + DEX + LY294002, and LPS + DEX + BEZ235groups. Lung samples were collected 48 h after LPS treatment. Results DEX significantly inhibited LPS-induced increases in the lung weight/body weight ratio and lung wet/dry weight ratio, decreased inflammatory cell infiltration, and decreased the production of proinflammatory factors, such as interleukin-1β (IL-1β), IL-6, and tumor necrosis factor α (TNF-α)in the lungs. DEX also markedly attenuated the increases in malondialdehyde 5 (MDA 5) and inositol-dependent enzyme a (IRE-a), attenuated the decrease in superoxide dismutase 1(SOD-1), reversed the low expression of B-cell lymphoma-2 (Bcl-2), and the high expressions of Bax and Caspase-3. DEX also decreased the expression of phosphorylated PI3K and phosphorylated Akt and increased the expression of phosphorylated forkhead box-O transcription factor 1 (FoxO1). More interestingly, LY294002 or BEZ235 pretreatment significantly abolished the inhibitory effects of DEX on LPS-induced lung inflammation, oxidative stress, and apoptosis. Conclusions These data suggest that DEX ameliorates LPS-induced acute lung injury partly through the PI3K/Akt/FoxO1 signaling pathway.

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Section: Discussionsupporting

confidence: 92%

Dexmedetomidine ameliorates lipopolysaccharide-induced acute lung injury by inhibiting the PI3K/Akt/FoxO1 signaling pathway

Cui

Zhang

2021

J Anesth

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“…Due to ET stimulation, Kupffer cells secrete a large number of active mediators, including cytokines such as IL-1β, IL-6, TNF-α, and reactive oxygen species (ROS). This also results in elevated hepatic function markers, eventually triggering the liver damage (Sato et al, 2016;Xie et al, 2019;Zou et al, 2020). In this study, serum IL-1β and IL-6 were increased in BDL rats and were reduced by RF.…”

Section: Discussionmentioning

confidence: 50%

Better detoxifying effect of ripe forsythiae fructus over green forsythiae fructus and the potential mechanisms involving bile acids metabolism and gut microbiota

Wang

Qin

et al. 2022

Front. Pharmacol.

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Forsythiae Fructus (FF), the fruit of Forsythia suspensa (Thunb.) Vahl. (Lianqiao), is one of the most fundamental herbs in Traditional Chinese Medicines (TCM), mainly due to its heat-clearing and detoxifying effects. There are two types of FF, the greenish fruits that start to ripen (GF) and the yellow fruits that are fully ripe (RF), called “Qingqiao” and “Laoqiao” referred to the Chinese Pharmacopoeia, respectively. It undergoes a complex series of changes during the maturation of FF. However, the clinical uses and preparation of phytopharmaceuticals of FF have not been distinguished to date. Moreover, there is limited information on the study of the difference in pharmacological activity between RF and GF. In this study, a rat model of bile duct ligation (BDL)-induced cholestasis was used to compare the differences in their effects. RF was found to have better results than GF in addressing toxic bile acids (BAs) accumulation and related pathological conditions caused by BDL. The underlying mechanism may be related to the interventions of gut microbiota. The results of the present study suggest that the better detoxifying effect of RF than GF may be indirectly exerted through the regulation of gut microbiota and thus the improvement of BAs metabolism.

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“…The data showed that high doses of Dex at 10 µg/kg/h significantly decreased expression of the inflammation-related cytokines IL-1β, il-6 and TnF-α, W/d ratios and pathological changes in the Vili model rats. Several reports have demonstrated that dex reduces the apoptosis of various parenchymal and epithelial cells following inflammation or ischemia (30)(31)(32)(33). Similarly, H-Dex was found to significantly reduce alveolar epithelial cell apoptosis.…”

Section: Discussionmentioning

confidence: 86%

Dexmedetomidine reduces ventilator-induced lung injury via ERK1/2 pathway activation

Zhu

Ben-qing

et al. 2020

Mol Med Rep

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Mechanical ventilation (MV) can contribute to ventilator-induced lung injury (Vili); dexmedetomidine (dex) treatment attenuates MV-related pulmonary inflammation, but the mechanisms remain unclear. Therefore, the present study aimed to explore the protective effect and the possible molecular mechanisms of dex in a Vili rodent model. adult male Sprague-dawley rats were randomly assigned to one of seven groups (n=24 rats/group). rats were euthanized after 4 h of continuous MV, and pathological changes, lung wet/dry (W/D) weight ratio, the levels of inflammatory cytokines (il-1β, TnF-α and il-6) in the bronchoalveolar lavage fluid (BALF), and the expression levels of Bcl-2 homologous antagonist/killer (Bak), Bcl-2, pro-caspase-3, cleaved caspase-3 and the phosphorylation of erK1/2 in the lung tissues were measured. Propidium iodide uptake and Tunel staining were used to detect epithelial cell death. The dex pretreatment group exhibited fewer pathological changes, lower W/d ratios and lower expression levels of inflammatory cytokines in BALF compared with the VILI group. Dex significantly attenuated the ratio of Bak/Bcl-2, cleaved caspase-3 expression levels and epithelial cell death, and increased the expression of phosphorylated erK1/2. The protective effects of dex could be partially reversed by Pd98059, which is a mitogen-activated protein kinase (upstream of erK1/2) inhibitor. overall, dexmedetomidine was found to reduce the inflammatory response and epithelial cell death caused by Vili, via the activation of the erK1/2 signaling pathway.

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Dexmedetomidine activates the PI3K/Akt pathway to inhibit hepatocyte apoptosis in rats with obstructive jaundice

Cited by 4 publications

References 28 publications

Dexmedetomidine ameliorates lipopolysaccharide-induced acute lung injury by inhibiting the PI3K/Akt/FoxO1 signaling pathway

Dexmedetomidine ameliorates lipopolysaccharide-induced acute lung injury by inhibiting the PI3K/Akt/FoxO1 signaling pathway

Better detoxifying effect of ripe forsythiae fructus over green forsythiae fructus and the potential mechanisms involving bile acids metabolism and gut microbiota

Dexmedetomidine reduces ventilator-induced lung injury via ERK1/2 pathway activation

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