Effect of dexmedetomidine, midazolam, and propofol on lipopolysaccharide‑stimulated dendritic cells

Guo, Feng; Ding, Ying; Yu, Xue; Cai, Xiujun

doi:10.3892/etm.2018.6094

Cited by 6 publications

(8 citation statements)

References 40 publications

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“…In the present study however, we generated a dose response curve for DEX, ranging from 0.01 to 10 µM and identified a concentration of 1 µM to be the least cytotoxic. As this concentration is generally used in the clinic 39 , our data thus endorse it to be potentially safer in humans. Data presented in this study are also consistent with earlier work completed by Wu et al which demonstrated that DEX protected neurons against apoptosis, axonal degradation, and synaptic degeneration after traumatic brain injury in a murine model 28 .…”

Section: Discussionsupporting

confidence: 56%

“…To avoid confounders of the whole animal or intact brain slices, we used a well-established in vitro cell culture model 33 . 1 to 2.5 μM has been recommended as a clinically relevant DEX concentration for in vitro experiments, and 5 μM deemed to be a higher dose in the clinical domain 39 . In the present study, we tested for the first time, all of the above concentrations to obtain a more comprehensive dose–response curve.…”

Section: Resultsmentioning

confidence: 99%

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Dexmedetomidine does not compromise neuronal viability, synaptic connectivity, learning and memory in a rodent model

Jimenez-Tellez

Iqbal

Pehar

et al. 2021

Sci Rep

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Recent animal studies have drawn concerns regarding most commonly used anesthetics and their long-term cytotoxic effects, specifically on the nervous tissue. It is therefore imperative that the search continues for agents that are non-toxic at both the cellular and behavioural level. One such agent appears to be dexmedetomidine (DEX) which has not only been found to be less neurotoxic but has also been shown to protect neurons from cytotoxicity induced by other anesthetic agents. However, DEX’s effects on the growth and synaptic connectivity at the individual neuronal level, and the underlying mechanisms have not yet been fully resolved. Here, we tested DEX for its impact on neuronal growth, synapse formation (in vitro) and learning and memory in a rodent model. Rat cortical neurons were exposed to a range of clinically relevant DEX concentrations (0.05–10 µM) and cellular viability, neurite outgrowth, synaptic assembly and mitochondrial morphology were assessed. We discovered that DEX did not affect neuronal viability when used below 10 µM, whereas significant cell death was noted at higher concentrations. Interestingly, in the presence of DEX, neurons exhibited more neurite branching, albeit with no differences in corresponding synaptic puncta formation. When rat pups were injected subcutaneously with DEX 25 µg/kg on postnatal day 7 and again on postnatal day 8, we discovered that this agent did not affect hippocampal-dependent memory in freely behaving animals. Our data demonstrates, for the first time, the non-neurotoxic nature of DEX both in vitro and in vivo in an animal model providing support for its utility as a safer anesthetic agent. Moreover, this study provides the first direct evidence that although DEX is growth permissive, causes mitochondrial fusion and reduces oxygen reactive species production, it does not affect the total number of synaptic connections between the cortical neurons in vitro.

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Section: Discussionsupporting

confidence: 56%

Section: Resultsmentioning

confidence: 99%

Dexmedetomidine does not compromise neuronal viability, synaptic connectivity, learning and memory in a rodent model

Jimenez-Tellez

Iqbal

Pehar

et al. 2021

Sci Rep

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“…Deep sedation is thought to arise at plasma concentrations above 1.9 ng/mL [48,48]. Another study reported that 0.1, 1, and 10 μM of dexmedetomidine are high concentrations for clinical use, and 0.001 μM of dexmedetomidine is the lowest concentration for clinical use [50]. Therefore, the concentration of dexmedetomidine used in this study fall within the concentration range used in the clinics.…”

Section: Discussionmentioning

confidence: 55%

Anti-inflammatory effects of dexmedetomidine on human amnion-derived WISH cells

et al. 2020

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Background: To maintain the normal pregnancy, suppression of inflammatory signaling pathway is a crucial physiologic response. Dexmedetomidine has been used for labor analgesia or supplement of inadequate regional analgesia during delivery. And it has been reported that dexmedetomidine has an anti-inflammatory effect. In this study, we examined the influence of dexmedetomidine on the expression of cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2) and inflammatory cytokines in lipopolysaccharide (LPS)-stimulated human amnion-derived WISH cells. In addition, we evaluated the association of mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) pathway in anti-inflammatory effect of dexmedetomidine. Methods: Human amnion-derived WISH cells were pretreated with various concentrations of dexmedetomidine (0.001-1 µg/ml) for 1 h and after then treated with LPS (1 µg/ml) for 24 h. MTT assay was conducted to evaluate the cytotoxicity. Nitric oxide (NO) production was analyzed using Griess-reaction microassay. RT-PCR was performed for analysis of mRNA expressions of COX-2, PGE2, tumor necrosis factor (TNF)-α and interlukin (IL)-1β. Protein expressions of COX-2, PGE2, p38 and NF-κB were analyzed by western blotting. Results: LPS and dexmedetomidine had no cytotoxic effect on WISH cells. There was no difference in NO production after dexmedetomidine pretreatment. The mRNA and protein expressions of COX-2 and PGE2 were decreased by dexmedetomidine pretreatment in LPS-treated WISH cells. Dexmedetomidine also attenuated the LPS-induced mRNA expression of TNF-α and IL-1β. The activation of p38 and NF-κB was suppressed by dexmedetomidine pretreatment in LPS-treated WISH cells. Conclusion: We demonstrated that dexmedetomidine pretreatment suppressed the expressions of inflammatory mediators increased by LPS. In addition, this study suggests that anti-inflammatory effect of dexmedetomidine on WISH cells was mediated by the inhibitions of p38 and NF-κB activation.

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“…Leukotrienes are comprised a class of vital cytokines that can accelerate the growth of human cancer cells [ 20 , 21 ]. Propofol exerts an anticancer affect by altering the function of dendritic cells [ 22 ] and has been reported to prevent the proliferation and metastasis of multiple cancers. For example, propofol was shown to prevent the progress of pancreatic cancer under hypoxic conditions via ADAM8 [ 23 ] and affect the proliferation and apoptosis of cardia cancer cells via the MAPK/ERK signaling pathway [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Propofol Prevents the Growth, Migration, Invasion, and Glycolysis of Colorectal Cancer Cells by Downregulating Lactate Dehydrogenase Both In Vitro and In Vivo

Wang

Shi

et al. 2022

Journal of Oncology

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Colorectal cancer (CRC) is one of the most frequently diagnosed gastrointestinal malignancies worldwide and has high rates of morbidity and mortality. Propofol has been reported to have certain anticancer properties. However, the role and mechanism of propofol in CRC are not entirely clear. CRC cells were treated with propofol and/or LDH-overexpression plasmids, and a mouse xenograft model of CRC was also established and treated with propofol. Cell viability, migration, and invasion were evaluated by CCK-8, wound healing, and transwell assays; the expression of related proteins was confirmed by western blotting; indexes of the glycolytic pathway were analyzed using specialized kits; tumor growth in mice was measured; pathological tissue structure was assessed by H&E staining; and 8-OHDG expression was determined by an immunochemistry assay. Our results verified that propofol could effectively prevent the malignant behaviors of CRC cells by suppressing cell viability, migration, and invasion and accelerating apoptosis. We also discovered that propofol could attenuate the glycolytic pathway in CRC cells. Moreover, we proved that lactate dehydrogenase (LDH) was required for the inhibitory effects of propofol on the growth of CRC cells, including glycolysis in CRC cells. Furthermore, our results showed that propofol could not only significantly inhibit tumor growth and glycolysis, but also ameliorate the pathological structure of CRC tumors. The current results proved that propofol could attenuate the malignant progression of CRC by preventing LDH activity, suggesting that propofol might be an effective therapeutic agent for CRC.

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Effect of dexmedetomidine, midazolam, and propofol on lipopolysaccharide‑stimulated dendritic cells

Abstract: Abstract. Dexmedetomidine, midazolam and propofol are common sedative drugs used in the intensive care unit.

Cited by 6 publications

References 40 publications

Dexmedetomidine does not compromise neuronal viability, synaptic connectivity, learning and memory in a rodent model

Dexmedetomidine does not compromise neuronal viability, synaptic connectivity, learning and memory in a rodent model

Anti-inflammatory effects of dexmedetomidine on human amnion-derived WISH cells

Propofol Prevents the Growth, Migration, Invasion, and Glycolysis of Colorectal Cancer Cells by Downregulating Lactate Dehydrogenase Both In Vitro and In Vivo

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