3-Methyladenine and dexmedetomidine reverse lipopolysaccharide-induced acute lung injury through the inhibition of inflammation and autophagy

Ding, Dengfeng; Xu, Shiyuan; Zhang, Hongfei; Zhao, Wei; Zhang, Xueping; Jiang, Yibin; Wang, Ping; Dai, Zhongliang; Zhang, Junzhi

doi:10.3892/etm.2018.5832

Cited by 21 publications

(19 citation statements)

References 31 publications

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“…22 Previous animal model studies have reported that DEX has a lung-protective effect involving IL-6 inhibition and endothelin-induced inflammatory reaction. [23][24][25] We observed that DEX decreases the plasma and lung tissue levels of IL-6 and TNF-α during the perioperative period. DEX partially attenuates lung injury by activating PI3K/Akt/HIF-1α signaling pathway and significantly reduces serum inflammatory cytokine levels in rat models of obstructive jaundice.…”

Section: Discussionmentioning

confidence: 83%

<p>Activation of PI3K/Akt/HIF-1α Signaling is Involved in Lung Protection of Dexmedetomidine in Patients Undergoing Video-Assisted Thoracoscopic Surgery: A Pilot Study</p>

Zhu

Zhang

et al. 2020

DDDT

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Background: Lung resection and one lung ventilation (OLV) during video-assisted thoracoscopic surgery (VATS) may lead to acute lung injury. Dexmedetomidine (DEX), a highly selective α 2 adrenergic receptor agonist, improves arterial oxygenation in adult patients undergoing thoracic surgery. The aim of this pilot study was to explore possible mechanism related to lung protection of DEX in patients undergoing VATS. Patients and Methods: Seventy-four patients scheduled for VATS were enrolled in this study. Three timepoints (before anesthesia induction (T 0), 40 min after OLV (T 1), and 10 min after two-lung ventilation (T 2)) of arterial blood gas were obtained. Meanwhile, lung histopathologic examination, immunohistochemistry analysis (occludin and ZO-1), levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in lung tissue and plasma, and activation of phosphoinositide-3-kinase (PI3K)/AKT/hypoxia-inducible factor (HIF)-1α signaling were detected. Postoperative outcomes including duration of withdrawing the pleural drainage tube, length of hospital stay, hospitalization expenses, and postoperative pulmonary complications (PPCs) were also recorded. Results: Sixty-seven patients were randomly divided into DEX group (group D, n=33) and control group (group N, n=34). DEX improved oxygenation at T 1 and T 2 (group D vs group N; T 1 : 191.8 ± 49.8 mmHg vs 159.6 ± 48.1 mmHg, P = 0.009; T 2 : 406.0 mmHg [392.2-423.7] vs 374.5 mmHg [340.2-378.2], P = 0.001). DEX alleviated the alveolar capillary epithelial structure damage, increased protein expression of ZO-1 and occludin, inhibited elevation of the expression of TNF-α and IL-6 in lung tissue and plasma, and increased protein expression of p-PI3K, p-AKT and HIF-1α. Dex administered had better postoperative outcomes with less risk of PPCs and hospitalization expenses as well as shorter duration of withdrawing the pleural drainage tube and length of hospital stay. Conclusion: Activation of PI3K/Akt/HIF-1α signaling might be involved in lung protection of DEX in patients undergoing VATS.

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Section: Discussionmentioning

confidence: 83%

<p>Activation of PI3K/Akt/HIF-1α Signaling is Involved in Lung Protection of Dexmedetomidine in Patients Undergoing Video-Assisted Thoracoscopic Surgery: A Pilot Study</p>

Zhu

Zhang

et al. 2020

DDDT

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“…The present data indicated that oxaliplatin injection could increase the levels of LPS in the serum and DRG of mice, which was decreased following treatment with hydrogen-rich water; however, these differences were not reflected in the spinal cords. Since TLR4 is a ligand of LPS, 33 TLR4 was further examined, and the result was the same as that for LPS ( Figure 7 ). It can therefore be inferred that hydrogen-rich water affects the gut microbiota and reduces the occurrence of oxaliplatin-induced CINP through the LPS-TLR4 pathway.…”

Section: Discussionmentioning

confidence: 99%

Drinking Hydrogen-Rich Water Alleviates Chemotherapy-Induced Neuropathic Pain Through the Regulation of Gut Microbiota

Lian¹,

Shen²,

Zhang³

et al. 2021

JPR

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Introduction Chemotherapy-induced neuropathic pain (CINP) is one of the most common complications of chemotherapeutic drugs which limits the dose and duration of potentially life-saving anticancer treatment and compromises the quality of life of patients. Our previous studies have reported that molecular hydrogen (H 2 ) can be used to prevent and treat various diseases. But the underlying mechanism remains unclear. The aim of the present study was to explore the effects of hydrogen-rich water on gut microbiota in CINP. Methods All C57BL/6J mice were divided into 4 groups: The group fed with normal drinking water and injected with saline (H 2 O + Saline), the group fed with normal drinking water and injected with oxaliplatin (H 2 O + OXA), the group fed with hydrogen-rich water and injected with saline (HW + Saline), and the group fed with hydrogen-rich water and injected with oxaliplatin (HW + OXA). The mechanical paw withdrawal threshold of the mice was tested on days 0, 5, 10, 15 and 20 after hydrogen-rich water treatment. On day 20, feces of mice from different groups were collected for microbial community diversity and structure analysis. The levels of inflammatory cytokines (TNF-α and IL-6), oxidative stress factors (OH - and ONOO - ), lipopolysaccharide (LPS) and Toll-like receptor 4 (TLR4) were detected in dorsal root ganglia (DRG), L4-6 spinal cord segments and serum by enzyme-linked immunosorbent assay. The expression of TLR4 in DRG and spinal cords was determined by Western blot. Results The results illustrated that hydrogen-rich water could alleviate oxaliplatin-induced hyperalgesia, reduce the microbial diversity and alter the structure of gut microbiota, reverse the imbalance of inflammatory cytokines and oxidative stress, and decrease the expression of LPS and TLR4. Conclusion Hydrogen-rich water may alleviate CINP by affecting the diversity and structure of the gut microbiota, and then the LPS-TLR4 pathway, which provides a direction for further research.

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“…For instance, with the application of autophagy inhibitors, the expression of inflammatory genes is enhanced in adipocytes; conversely, activation of autophagy reduces the expression of inflammatory genes, indicating that autophagy can balance the inflammatory response [21]. In contrast, with the autophagy inhibitors, 3-methyladenine blocked autophagy activity and reversed LPS-induced acute lung injury through the inhibition of inflammation and autophagy [22]. These observations indicated that the protective or detrimental effect of autophagy activation depends on cell types, stimuli, and environment, and the directionality of the effect may be context dependent.…”

Section: Introductionmentioning

confidence: 99%

Punicalagin Prevents Inflammation in LPS- Induced RAW264.7 Macrophages by Inhibiting FoxO3a/Autophagy Signaling Pathway

et al. 2019

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Punicalagin, a hydrolysable tannin of pomegranate juice, exhibits multiple biological effects, including inhibiting production of pro-inflammatory cytokines in macrophages. Autophagy, an intracellular self-digestion process, has been recently shown to regulate inflammatory responses. In this study, we investigated the anti-inflammatory potential of punicalagin in lipopolysaccharide (LPS) induced RAW264.7 macrophages and uncovered the underlying mechanisms. Punicalagin significantly attenuated, in a concentration-dependent manner, LPS-induced release of NO and decreased pro-inflammatory cytokines TNF-α and IL-6 release at the highest concentration. We found that punicalagin inhibited NF-κB and MAPK activation in LPS-induced RAW264.7 macrophages. Western blot analysis revealed that punicalagin pre-treatment enhanced LC3II, p62 expression, and decreased Beclin1 expression in LPS-induced macrophages. MDC assays were used to determine the autophagic process and the results worked in concert with Western blot analysis. In addition, our observations indicated that LPS-induced releases of NO, TNF-α, and IL-6 were attenuated by treatment with autophagy inhibitor chloroquine, suggesting that autophagy inhibition participated in anti-inflammatory effect. We also found that punicalagin downregulated FoxO3a expression, resulting in autophagy inhibition. Overall these results suggested that punicalagin played an important role in the attenuation of LPS-induced inflammatory responses in RAW264.7 macrophages and that the mechanisms involved downregulation of the FoxO3a/autophagy signaling pathway.

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3-Methyladenine and dexmedetomidine reverse lipopolysaccharide-induced acute lung injury through the inhibition of inflammation and autophagy

Cited by 21 publications

References 31 publications

<p>Activation of PI3K/Akt/HIF-1α Signaling is Involved in Lung Protection of Dexmedetomidine in Patients Undergoing Video-Assisted Thoracoscopic Surgery: A Pilot Study</p>

<p>Activation of PI3K/Akt/HIF-1α Signaling is Involved in Lung Protection of Dexmedetomidine in Patients Undergoing Video-Assisted Thoracoscopic Surgery: A Pilot Study</p>

Drinking Hydrogen-Rich Water Alleviates Chemotherapy-Induced Neuropathic Pain Through the Regulation of Gut Microbiota

Punicalagin Prevents Inflammation in LPS- Induced RAW264.7 Macrophages by Inhibiting FoxO3a/Autophagy Signaling Pathway

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