Subanesthetic isoflurane relieves zymosan-induced neutrophil inflammatory response by targeting NMDA glutamate receptor and Toll-like receptor 2 signaling

Li, Jun-Tang; Wang, Weiqi; Wang, Ling; Liu, Ningning; Zhao, Yali; Zhu, Xiaoshan; Liu, Qinqin; Gao, Chunfang; Yang, Angang; Jia, Lintao

doi:10.18632/oncotarget.9091

Cited by 12 publications

(15 citation statements)

References 56 publications

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“…However, NO also activates protein kinase G (PKG), through the NO/cyclic guanosine monophosphate/PKG pathway ( 45 ). Additionally, phosphorylated p38 mitogen-activated protein kinase activates caspase-3 ( 46 ). Caspase-3, which serves as an intersection of the endogenous and exogenous apoptotic pathways, is the main protein with apoptotic activity ( 47 ).…”

Section: Discussionmentioning

confidence: 99%

Effects of simvastatin on iNOS and caspase‑3 levels and oxidative stress following smoke inhalation injury

Yang

Guo

et al. 2020

Mol Med Rep

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The overexpression of inducible nitric oxide synthase (inoS) induces cell apoptosis through various signal transduction pathways and aggravates lung injury. caspase-3 is an important protein in the apoptotic pathway and its activation can exacerbate apoptosis. Simvastatin, a hydroxymethyl glutaryl-a reductase inhibitor, protects against smoke inhalation injury by inhibiting the synthesis and release of inflammatory factors and decreasing cell apoptosis. Following the establishment of an animal model of smoke inhalation injury, lung tissue and serum were collected at different time points and the protein and mrna expression of inoS and caspase-3 in lung tissue by immunochemistry, western blot and reverse transcription-quantitative polymerase chain reaction, the malondialdehyde (Mda) content and superoxide dismutase (Sod) activity in lung tissue and serum were analyzed using thiobarbituric acid method and the WST-1 method. The results were statistically analyzed. The lung tissues of the rats in the saline group and the low-, middle-and high-dose groups exhibited clear edema and hemorrhage, and had significantly higher pathological scores at the various time points compared with the rats in the control group (P<0.05). Furthermore, lung tissue and serum samples obtained from these four groups had significantly higher mRNA and protein expression levels of iNOS and caspase-3 (P<0.05), significantly lower SOD activity and higher Mda content (P<0.05). compared with the saline group, the low-, middle-and high-dose groups had significantly lower pathological scores (P<0.05), significantly lower mrna and protein expression levels of inoS, caspase-3 and MDA content in lung tissues (P<0.05) and significantly higher Sod activity in lung tissues and serum. The middle-and high-dose groups had significantly lower pathological scores (P<0.05), significantly decreased iNOS and caspase-3 mRNA and protein expression in lung tissues, significantly higher SOD activity in lung tissues and serum and a significantly lower Mda content (P<0.05) compared with the low-dose group. With the exception of Sod activity in lung tissues at 24 and 72 h and MDA content in serum at 48 h, no significant differences were observed between the middle-and high-dose groups. The present study demonstrated that there was an association between the therapeutic effect and dosage of simvastatin within a definitive range. In rats with smoke inhalation injury, simvastatin inhibited inoS and caspase-3 expression in lung tissues and mitigated oxidative stress, thereby exerting a protective effect. in addition, the effect and dose were associated within a definitive range.

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Section: Discussionmentioning

confidence: 99%

Effects of simvastatin on iNOS and caspase‑3 levels and oxidative stress following smoke inhalation injury

Yang

Guo

et al. 2020

Mol Med Rep

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“…DM and its metabolite DX binding at sigma-1 receptors with high affinities at nanomolar (nM) range [31] and with lower affinities on NMDA receptors at micromolar (M) range [27,28,30] in vitro and in rodent brain. Previous studies had showed that in RBCs [32] and neutrophils [33], NMDA receptor activity were found. And the sigma-1 receptors were also found in human plasma [34], leukocytes [35] and lymphocytes [36].…”

Section: Discussionmentioning

confidence: 92%

Dextromethorphan Protect the Valproic Acid Induced Downregulation of Neutrophils in Patients with Bipolar Disorder

Chang

Lee

et al. 2020

Clin Psychopharmacol Neurosci

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Objective: Valproic acid (VPA) is an anticonvulsant and commonly long term used as a mood stabilizer for patients with mood disorders. However its chronic effects on the hematological changes were noticed and need to be further evaluated. In this study, we evaluated, in Taiwanese Han Chinese patients with bipolar disorders (BD), the chronic effects of VPA or VPA plus dextromethorphan (DM) on the hematological molecules (white blood cell [WBCs], red blood cells [RBCs], hemoglobin, hematocrit, and platelets). Methods: In a 12-week, randomized, double-blind study, we randomly assigned BD patients to one of three groups: VPA plus either placebo (VPA＋P, n = 57) or DM (30 mg/day, VPA＋DM30, n = 56) or 60 mg/day (VPA＋DM60, n = 53). The Young Mania Rating Scale and Hamilton Depression Rating Scale were used to evaluate symptom severity, and the hematological molecules were checked. Results: Paired t test showed that the WBC, neutrophils, platelets and RBCs were significantly lowered after 12 weeks of VPA＋P or VPA＋DM30 treatment. VPA＋DM60 represented the protective effects in the WBCs, neutrophils, and RBCs but not in the platelets. We further calculated the changes of each hematological molecules after 12 weeks treatment. We found that combination use of DM60 significantly improved the decline in neutrophils induced by the long-term VPA treatment. Conclusion: Hematological molecule levels were lower after long-term treatment with VPA. VPA＋DM60, which yielded the protective effect in hematological change, especially in the neutrophil counts. Thus, DM might be adjunct therapy for maintaining hematological molecules in VPA treatment.

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“…These data consistently indicated that Zymosan-A induced radioprotective effects via TLR2 but not TLR4. Many studies indicated that Zymosan-A can induce NF-κB phosphorylation and nuclear translocation by targeting TLR2[21, 22, 29]. Zymosan-A can also upregulate cytokines, including TNF-α; the IL-1 family; the IL-6, IL-8, and IL-10 family; IL-11; IL-23; the IL-12 family; IL-15; TGF-β; and G-CSF[30-34].…”

Section: Discussionmentioning

confidence: 99%

Zymosan-a Protects the Hematopoietic System from Radiation-Induced Damage by Targeting TLR2 Signaling Pathway

Cheng

Dong

et al. 2017

Cell Physiol Biochem

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Background/Aims: The hematopoietic system is vulnerable to ionizing radiation and is often severely damaged by radiation. Molecules affecting radioresistance include Toll-like receptor 2. We investigated whether Zymosan-A, a novel TLR2 agonist, can protect the hematopoietic system from radiation-induced damage after total body irradiation. Methods: Mice were exposed to total body radiation after treatment with Zymosan-A or normal saline, and their survival was recorded. Tissue damage was evaluated by hematoxylin–eosin staining. The number of nucleated cells in bone marrow was determined by flow cytometry. Cell viability and apoptosis assay were determined by CCK-8 assay and flow cytometry assay. Enzyme-linked immunosorbent assay was used to detect the level of cytokines. Results: Zymosan-A protected mice from radiation-induced death and prevented radiation-induced hematopoietic system damage. Zymosan-A also promoted cell viability and inhibited cell apoptosis caused by radiation, induced radioprotective effects via TLR2, upregulated IL-6, IL-11, IL-12, and TNF-α in vivo. Conclusion: Zymosan-A can provide protection against radiation-induced hematopoietic system damage by targeting the TLR2 signaling pathway. Thus, Zymosan-A can be potentially effective radioprotectant.

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Subanesthetic isoflurane relieves zymosan-induced neutrophil inflammatory response by targeting NMDA glutamate receptor and Toll-like receptor 2 signaling

Cited by 12 publications

References 56 publications

Effects of simvastatin on iNOS and caspase‑3 levels and oxidative stress following smoke inhalation injury

Effects of simvastatin on iNOS and caspase‑3 levels and oxidative stress following smoke inhalation injury

Dextromethorphan Protect the Valproic Acid Induced Downregulation of Neutrophils in Patients with Bipolar Disorder

Zymosan-a Protects the Hematopoietic System from Radiation-Induced Damage by Targeting TLR2 Signaling Pathway

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