Tetramethylpyrazine Showed Therapeutic Effects on Sepsis-Induced Acute Lung Injury in Rats by Inhibiting Endoplasmic Reticulum Stress Protein Kinase RNA-Like Endoplasmic Reticulum Kinase (PERK) Signaling-Induced Apoptosis of Pulmonary Microvascular Endothelial Cells

Liu, Wensheng; Liu, Kaizhong; Zhang, Shu; Shan, Lihong; Tang, Jiangfeng

doi:10.12659/msm.908616

Cited by 30 publications

(21 citation statements)

References 21 publications

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“…It was reported that the endoplasmic reticulum (ER) stress-inducible transcription factor CHOP induced cell death and was an important factor in the pathogenesis of different disease mouse models [ 19 , 38 , 39 , 40 , 41 , 42 ]. To investigate the effect of Mito-T on the expression of CHOP after APAP-induced liver injury, Mito-T (20 mg/kg, i.p.)…”

Section: Resultsmentioning

confidence: 99%

The Late-Stage Protective Effect of Mito-TEMPO against Acetaminophen-Induced Hepatotoxicity in Mouse and Three-Dimensional Cell Culture Models

et al. 2020

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An overdose of acetaminophen (APAP), the most common cause of acute liver injury, induces oxidative stress that subsequently causes mitochondrial impairment and hepatic necroptosis. N-acetyl-L-cysteine (NAC), the only recognized drug against APAP hepatotoxicity, is less effective the later it is administered. This study evaluated the protective effect of mitochondria-specific Mito-TEMPO (Mito-T) on APAP-induced acute liver injury in C57BL/6J male mice, and a three dimensional (3D)-cell culture model containing the human hepatoblastoma cell line HepG2. The administration of Mito-T (20 mg/kg, i.p.) 1 h after APAP (400 mg/kg, i.p.) injection markedly attenuated the APAP-induced elevated serum transaminase activity and hepatic necrosis. However, Mito-T treatment did not affect key factors in the development of APAP liver injury including the activation of c-jun N-terminal kinases (JNK), and expression of the transcription factor C/EBP homologous protein (CHOP) in the liver. However, Mito-T significantly reduced the APAP-induced increase in the hepatic oxidative stress marker, nitrotyrosine, and DNA fragmentation. Mito-T markedly attenuated cytotoxicity induced by APAP in the HepG2 3D-cell culture model. Moreover, liver regeneration after APAP hepatotoxicity was not affected by Mito-T, demonstrated by no changes in proliferating cell nuclear antigen formation. Therefore, Mito-T was hepatoprotective at the late-stage of APAP overdose in mice.

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Section: Resultsmentioning

confidence: 99%

The Late-Stage Protective Effect of Mito-TEMPO against Acetaminophen-Induced Hepatotoxicity in Mouse and Three-Dimensional Cell Culture Models

et al. 2020

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“…A large amount of bacteria and endotoxins in the intestinal tract invade the blood circulation through the portal vein and lymphatic system, causing intestinal infection, endotoxemia, and the activation of cytotoxic pathways, which eventually lead to multiple organ dysfunction syndrome. Lung injury often occurs early and develops fast, which is one of the most direct causes of death in patients with sepsis …”

Section: Introductionmentioning

confidence: 99%

Dachengqi decoction alleviates acute lung injury and inhibits inflammatory cytokines production through TLR4/NF‐κB signaling pathway in vivo and in vitro

Liu

2019

J of Cellular Biochemistry

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Background and Objectives: Sepsis that arises from uncontrolled pulmonary inflammation could induce acute lung injury (ALI), leading to the high death rate. Dachengqi decoction (DCQD) is a common traditional Chinese herbal medicine with strong anti-inflammatory effects. The current study aimed to explore the effect of DCQD on the inflammatory cytokines production, the aquaporin-1 (AQP-1) and AQP-5 protein expression in lipopolysaccharide (LPS)-induced ALI models, and the potential mechanisms underlying its effects.Methods: Sprague-Dawley rats and HULEC-5a cells were used as study models in the research. To detect related molecules in the study, the real-time polymerase chain reaction analysis, cell counting kit-8 assay, Western blot analysis, and enzyme-linked immunosorbent assay were performed.Results: DCQD could inhibit the expression of LPS-induced inflammatory cytokines, including interleukin-6 (IL-6), IL-8, and tumor necrosis factor-α (TNF-α), in lung tissues and could reduce pulmonary edema by upregulating the expression of AQP-1 and AQP-5 in rats with LPS-induced ALI. Moreover, the results suggested that the toll-like receptor 4 (TLR4)/NF-κB signaling is indispensable for DCQD to increase the expression of AQP-1 and AQP-5 and inhibits the production of IL-6, IL-8, and TNF-α in LPS-induced HULEC-5a cells. Conclusion:The results of our study suggested that DCQD suppresses the TLR4/NF-κB signaling pathway, increases the protein expression of AQP-1 and AQP-5, and inhibits the production of inflammatory cytokines, by which it may alleviate the inflammatory reactions in ALI and benefit the treatments. K E Y W O R D S acute lung injury (ALI), aquaporin-1 (AQP-1), aquaporin-5 (AQP-5), Dachengqi decoction (DCQD), inflammatory cytokines 1 | INTRODUCTION Acute lung injury (ALI), its severe complication, and pulmonary edema are acute and life-threatening diseases caused by a variety of factors, including trauma, pneumonia, shock, and sepsis; the high mortality rate remains unresolved. 1,2 A major cause of ALI is that the intestinal barrier function of patients with sepsis is often damaged. A large amount of bacteria and endotoxins in the intestinal tract invade the blood circulation through J Cell Biochem. 2019;120:8956-8964. wileyonlinelibrary.com/journal/jcb 8956 |

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“…It has been demonstrated that biomarkers in the plasma and BALF can be used to evaluate ALI severity ( 37 ). Decreased lung W/D ratio and protein content in BALF, together with increased PaO 2 , are indicators of attenuated ALI ( 38 , 39 ). According to the findings of the present study, ATRA markedly increased PaO 2 in arterial blood and reduced the protein content in BALF and lung W/D ratio in ALI rats, along with effectively alleviating pathological lung injury.…”

Section: Discussionmentioning

confidence: 99%

All‑trans retinoic acid promotes macrophage phagocytosis and decreases inflammation via inhibiting CD14/TLR4 in acute lung injury

Lei

et al. 2021

Mol Med Rep

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Acute lung injury (ALI) is a common clinical emergency and all-trans retinoic acid (ATRA) can alleviate organ injury. Therefore, the present study investigated the role of ATRA in ALI. Lipopolysaccharide (LPS)-induced ALI rats were treated with ATRA and the arterial partial pressure of oxygen (PaO 2 ), lung wet/dry weight (W/D) ratio and protein content in the bronchial alveolar lavage fluid (BALF) were measured to evaluate the effect of ATRA on ALI rats. Alveolar macrophages were isolated from the BALF. The phagocytic function of macrophages was detected using the chicken erythrocyte phagocytosis method and flow cytometry. The viability of macrophages was measured using a Cell Counting Kit-8 assay, and apoptosis was analyzed using a TUNEL assay and flow cytometry. The expression levels of Toll-like receptor 4 (TLR4) and cluster of differentiation (CD)14 on the macrophage membrane were detected by immunofluorescence staining. The protein levels of TLR4, CD14, phosphorylated (p)-65, p65, p-IκBα and IκBα were analyzed using western blotting. The concentrations of IL-6, IL-1β and macrophage inflammatory protein-2 in the plasma of rats were detected by ELISA. Macrophages were treated with IAXO-102 (TLR4 inhibitor) to verify the involvement of CD14/TLR4 in the effect of ATRA on ALI. ATRA provided protection against LPS-induced ALI, as evidenced by the increased PaO 2 and reduced lung W/D ratio and protein content in the BALF. ATRA enhanced macrophage phagocytosis and viability and reduced apoptosis and inflammation in ALI rats. Mechanically, ATRA inhibited CD14 and TLR4 expression and NF-κB pathway activation. ATRA enhanced macrophage phagocytosis and reduced inflammation by inhibiting the CD14/TLR4-NF-κB pathway in LPS-induced ALI. In summary, ATRA inactivated the NF-κB pathway by inhibiting the expression of CD14/TLR4 receptor in the alveolar macrophages of rats, thus enhancing the phagocytic function of macrophages in ALI rats, improving the activity of macrophages, inhibiting apoptosis, reducing the levels of inflammatory factors, and consequently playing a protective role in ALI model rats. This study may offer novel insights for the clinical management of ALI.

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Tetramethylpyrazine Showed Therapeutic Effects on Sepsis-Induced Acute Lung Injury in Rats by Inhibiting Endoplasmic Reticulum Stress Protein Kinase RNA-Like Endoplasmic Reticulum Kinase (PERK) Signaling-Induced Apoptosis of Pulmonary Microvascular Endothelial Cells

Cited by 30 publications

References 21 publications

The Late-Stage Protective Effect of Mito-TEMPO against Acetaminophen-Induced Hepatotoxicity in Mouse and Three-Dimensional Cell Culture Models

The Late-Stage Protective Effect of Mito-TEMPO against Acetaminophen-Induced Hepatotoxicity in Mouse and Three-Dimensional Cell Culture Models

Dachengqi decoction alleviates acute lung injury and inhibits inflammatory cytokines production through TLR4/NF‐κB signaling pathway in vivo and in vitro

All‑trans retinoic acid promotes macrophage phagocytosis and decreases inflammation via inhibiting CD14/TLR4 in acute lung injury

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