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Original Articles
- 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
- 7,294 View
- 162 Download
- 5 Web of Science
- 5 Crossref
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Abstract
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
- Exosomes Derived from ADSCs Attenuate Sepsis-Induced Lung Injury by Delivery of Circ-Fryl and Regulation of the miR-490-3p/SIRT3 Pathway
- Basic science and research
- Flecainide Improve Sepsis Induced Acute Lung Injury by Controlling Inflammatory Response
- Jia Song, Young joong Suh, Hyun jung Lee, Eun a Jang, Hong-beom Bae, Sang-Hyun Kwak
- Korean J Crit Care Med. 2016;31(3):194-201. Published online August 30, 2016
- DOI: https://doi.org/10.4266/kjccm.2016.00157
- 7,661 View
- 128 Download
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Abstract
PDF
- Background
Flecainide is an antiarrhythmic agent that is used primarily in the treatment of cardiac arrhythmias. Some evidences also suggest that flecainide can participate in alveolar fluid clearance and inflammatory responses. This experiment was aimed to evaluate the effects of flecainide on sepsis induced acute lung injury in a rat model.
Methods
Rats were treated with subcutaneous infusion of saline or flecainide (0.1 or 0.2 mg/kg/hr) by a mini-osmotic pump. Subcutaneous infusion was started 3 hours before and continued until 8 hours after intraperitoneal injection of saline or endotoxin. Animals were sacrificed for analyses of severity of acute lung injury with wet to dry (W/D) ratio and lung injury score (LIS) in lung and inflammatory responses with level of leukocyte, polymorphonuclear neutrophils (PMNs) and inteleukin-8 (IL-8) in bronchoalveolar lavages fluid (BALF).
Results
Flecainide markedly improved dose dependently sepsis induced acute lung injury as analysed by W/D ratio (from 2.24 ± 0.11 to 1.76 ± 0.09, p < 0.05) and LIS (from 3 to 1, p < 0.05), and inflammatory response as determined by leukocyte (from 443 ± 127 to 229 ± 95, p < 0.05), PMNs (from 41.43 ± 17.63 to 2.43 ± 2.61, p < 0.05) and IL-8 (from 95.00 ± 15.28 to 40.00 ± 10.21, p < 0.05) in BALF.
Conclusions
Flecanide improve sepsis induced acute lung injury in rats by controlling inflammatory responses.
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