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2 "Tran Duc Tin"
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Basic science and research
The effects of BMS-470539 on lipopolysaccharide-induced acute lung injury
Eun-A Jang, Jin-Young Kim, Tran Duc Tin, Ji-A Song, Seong-Heon Lee, Sang-Hyun Kwak
Acute Crit Care. 2019;34(2):133-140.   Published online May 31, 2019
DOI: https://doi.org/10.4266/acc.2019.00507
  • 7,439 View
  • 162 Download
  • 5 Web of Science
  • 5 Crossref
AbstractAbstract PDF
Background
Overactivation of inflammatory cells, including macrophages and neutrophils, is associated with acute lung injury. BMS-470539 is a selective agonist of melanocortin 1 receptor, which triggers the inhibition of proinflammatory responses, suppressing neutrophil infiltration and protecting tissue. This study evaluated the effects of BMS-470539 on lipopolysaccharide-induced acute lung injury in a mouse model.
Methods
Mice received a subcutaneous injection of saline or BMS-470539 (18.47 mg/kg) 1 hour before an intratracheal injection of saline or lipopolysaccharide (20 μg). Mice were sacrificed to analyze the severity of pulmonary edema (lung wet-to-dry weight [W/D] ratio) and inflammatory responses (level of leukocytes, polymorphonuclear neutrophils [PMNs] and tumor necrosis factor alpha [TNF-α] in bronchoalveolar lavage fluid [BALF]), and neutrophil infiltration (myeloperoxidase activity). TNF-α activation was also measured in neutrophils from bone marrow. Survival was investigated in a second-hit sepsis mouse model.
Results
BMS-470539 improved sepsis-induced pulmonary edema, as demonstrated by a decreased W/D ratio (5.76%±0.83% to 3.81%±0.86%, P<0.05). The inflammatory response also improved, as shown by decreased levels of leukocytes (551±116 to 357±86×10²/mm³, P<0.05), PMNs (51.52%±16.23% to 18.41%±7.25%, P<0.01), and TNF-α (550±338 to 128±52 pg/ml, P<0.01) in the BALF. BMS-470539 also improved the inflammatory response, as shown by TNF-α levels (850±158 to 423±59 pg/ml, P<0.01) in neutrophils. BMS-470539 downregulated neutrophil infiltration in the lung (myeloperoxidase: 654±98 to 218±89 U/g, P<0.001). Lastly, BMS improved the survival rate (0% to 70%, P<0.01) in a mice multiple organ failure model.
Conclusions
BMS-470539 improved lipopolysaccharide-induced acute lung injury and mortality in mice by affecting the inflammatory response.

Citations

Citations to this article as recorded by  
  • Exosomes Derived from ADSCs Attenuate Sepsis-Induced Lung Injury by Delivery of Circ-Fryl and Regulation of the miR-490-3p/SIRT3 Pathway
    Weijun Shen, Xuan Zhao, Shitong Li
    Inflammation.2022; 45(1): 331.     CrossRef
  • Dichotomous Role of Tumor Necrosis Factor in Pulmonary Barrier Function and Alveolar Fluid Clearance
    Rudolf Lucas, Yalda Hadizamani, Perenlei Enkhbaatar, Gabor Csanyi, Robert W. Caldwell, Harald Hundsberger, Supriya Sridhar, Alice Ann Lever, Martina Hudel, Dipankar Ash, Masuko Ushio-Fukai, Tohru Fukai, Trinad Chakraborty, Alexander Verin, Douglas C. Eato
    Frontiers in Physiology.2022;[Epub]     CrossRef
  • NDP-MSH treatment recovers marginal lungs during ex vivo lung perfusion (EVLP)
    Caterina Lonati, Michele Battistin, Daniele E. Dondossola, Giulia A. Bassani, Daniela Brambilla, Riccardo Merighi, Patrizia Leonardi, Andrea Carlin, Marica Meroni, Alberto Zanella, Anna Catania, Stefano Gatti
    Peptides.2021; 141: 170552.     CrossRef
  • Antifibrotic and Anti-Inflammatory Actions of α-Melanocytic Hormone: New Roles for an Old Player
    Roshan Dinparastisaleh, Mehdi Mirsaeidi
    Pharmaceuticals.2021; 14(1): 45.     CrossRef
  • Activation of Melanocortin Receptors as a Potential Strategy to Reduce Local and Systemic Reactions Induced by Respiratory Viruses
    Caterina Lonati, Stefano Gatti, Anna Catania
    Frontiers in Endocrinology.2020;[Epub]     CrossRef
Infection
The Effects of Flecainide Acetate on Inflammatory-Immune Response in Lipopolysaccharide-Stimulated Neutrophils and on Mortality in Septic Rats
Shi Young Chung, Jinyoung Kim, Hong Bum Bae, Tran Duc Tin, Wan Ju, Sang Hyun Kwak
Acute Crit Care. 2018;33(1):34-41.   Published online February 28, 2018
DOI: https://doi.org/10.4266/acc.2017.00577
  • 7,660 View
  • 128 Download
  • 1 Web of Science
  • 1 Crossref
AbstractAbstract PDF
Background
Flecainide acetate is a drug used primarily for cardiac arrhythmia. Some studies also imply that flecainide acetate has the potential to regulate inflammatory-immune responses; however, its mechanism of action is contended. We determined the effects of flecainide acetate on lipopolysaccharide (LPS)-stimulated human neutrophils in vitro and on mortality in a septic rat model.
Methods
Neutrophils from human blood were cultured with varying concentrations of flecainide acetate (1 μM, 10 μM, or 100 μM) with or without LPS (100 ng/ml). To assess neutrophil activation, the protein levels of tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6 and IL-8 were measured after a 4-hour culture period. To assess the intracellular signaling pathways, the levels of phosphorylation of p38 mitogen-activated protein kinase (p38), extracellular signal-regulated kinase (ERK) 1/2, and c-Jun N-terminal kinase (JNK) were measured after a 30-minute culture period, and the nuclear translocation of nuclear factor (NF)-κB was measured after a 1-hour culture period. Additionally, the survival rate was investigated in a rat sepsis model.
Results
Flecainide acetate down-regulated the activation of proinflammatory cytokines, including TNF-α and IL-6 and IL-8, and intracellular signaling pathways including ERK 1/2 and NF-κB. Flecainide acetate also improved the survival rate in the rat sepsis model.
Conclusions
Collectively, these findings indicate that flecainide acetate can improve survival in a rat sepsis model by attenuating LPS-induced neutrophil responses. We therefore suggest that flecainide acetate plays an important role in modulating inflammatoryimmune responses.

Citations

Citations to this article as recorded by  
  • Persistence is key: unresolved immune dysfunction is lethal in both COVID-19 and non-COVID-19 sepsis
    Andy Y. An, Arjun Baghela, Peter Zhang, Reza Falsafi, Amy H. Lee, Uriel Trahtemberg, Andrew J. Baker, Claudia C. dos Santos, Robert E. W. Hancock
    Frontiers in Immunology.2023;[Epub]     CrossRef

ACC : Acute and Critical Care