The Effect of Modified Porcine Surfactant Alone or in Combination with Polymyxin B on Lung Homeostasis in LPS-Challenged and Mechanically Ventilated Adult Rats

M, Kolomazník; Kopincova, Jana; Nová, Zuzana; Topercerova, Juliana; Žila, Ivan; Mikolka, Pavol; Kosutova, Petra; Matasová, Katarína; Škovierová, Henrieta; Grendár, Marian; Mokrá, Daniela; Čalkovská, Andrea

doi:10.3390/molecules25194356

Cited by 5 publications

(6 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The dose chosen here was based on our pilot experiments in adult rats that have developed lung edema, local and systematic inflammation and oxidative stress after LPS 500 μg/kg of b.w. 34 .…”

Section: Discussionmentioning

confidence: 99%

Restoration of surfactant activity by polymyxin B in lipopolysaccharide-potentiated injury of immature rabbit lungs

Čalkovská

Haegerstrand-Björkman

Curstedt

2021

Sci Rep

Self Cite

View full text Add to dashboard Cite

During postnatal adaptation pulmonary surfactant may be inactivated by lipopolysaccharide (LPS). We evaluated the effect of surfactant therapy in combination with antibiotic polymyxin B (PxB) in double-hit model of neonatal lung injury. Surfactant (poractant alfa, Curosurf) was exposed to smooth (S) LPS without/with PxB and tested in captive bubble surfactometer. Preterm rabbits received intratracheally saline (control) or S-LPS and were ventilated with 100% oxygen. After 30 min, LPS-treated animals received no treatment, or surfactant (200 mg/kg) without/with 3% PxB; controls received the same dose of surfactant. Animals were ventilated for further 2 h. In vitro, addition of 5% S-LPS to surfactant increased minimum surface tension (γmin) and addition of 1–3% PxB to surfactant/S-LPS mixture restored γmin to low values. Animals only given S-LPS had lower lung compliance and lung gas volume (LGV) compared to surfactant groups. Treatment with surfactant/PxB, but not with surfactant only, restored LGV. Addition of PxB to the surfactant increased the alveolar expansion. S-LPS interferes with surface activity of the pulmonary surfactant and PxB improves the resistance of surfactant to LPS-induced inactivation. In our neonatal model of respiratory distress syndrome surfactant gives positive response even in simultaneous exposure to S-LPS, when enriched with PxB.

show abstract

Section: Discussionmentioning

confidence: 99%

Restoration of surfactant activity by polymyxin B in lipopolysaccharide-potentiated injury of immature rabbit lungs

Čalkovská

Haegerstrand-Björkman

Curstedt

2021

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…TLR-dependent pathway could possibly explain LPS-caused lung inflammation and subsequent alterations in SPs expression in ATII cells. In our experiments, at least 1.5-fold decrease was present in the expression level of all SPs in the lungs of rats with intratracheal LPS at the dose 500 μg/kg, while the administration of LPS at the dose 1000 μg/kg even further potentiated this effect [ 98 ].…”

Section: Alveolar Epithelial Type II Cellsmentioning

confidence: 92%

“…Very recently, the effect of endotoxin on clinically used modified porcine surfactant poractant alpha was analyzed. Results from in vitro experiments have shown that 1% LPS caused structural disarrangement of surfactant molecule, including disruption of lamellar structure, leading to inability to reach low surface tension [ 98 ].…”

Section: Alveolar Epithelial Type II Cellsmentioning

confidence: 99%

Alveolar-Capillary Membrane-Related Pulmonary Cells as a Target in Endotoxin-Induced Acute Lung Injury

Nová

Škovierová

Čalkovská

2019

IJMS

Self Cite

122

View full text Add to dashboard Cite

The main function of the lungs is oxygen transport from the atmosphere into the blood circulation, while it is necessary to keep the pulmonary tissue relatively free of pathogens. This is a difficult task because the respiratory system is constantly exposed to harmful substances entering the lungs by inhalation or via the blood stream. Individual types of lung cells are equipped with the mechanisms that maintain pulmonary homeostasis. Because of the clinical significance of acute respiratory distress syndrome (ARDS) the article refers to the physiological role of alveolar epithelial cells type I and II, endothelial cells, alveolar macrophages, and fibroblasts. However, all these cells can be damaged by lipopolysaccharide (LPS) which can reach the airspaces as the major component of the outer membrane of Gram-negative bacteria, and lead to local and systemic inflammation and toxicity. We also highlight a negative effect of LPS on lung cells related to alveolar-capillary barrier and their response to LPS exposure. Additionally, we describe the molecular mechanism of LPS signal transduction pathway in lung cells.

show abstract

“…The animals were instrumented in accordance with previous study [ 22 ]. All animals were placed on the heating plate regulated the temperature according to body temperature measured continuously in the rectum (Physitemp Instruments, Inc., TCAT-2LV, Clifton, NJ, USA).…”

Section: Methodsmentioning

confidence: 99%

N-Acetylcysteine in Mechanically Ventilated Rats with Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome: The Effect of Intravenous Dose on Oxidative Damage and Inflammation

Mikolka

Hanusrichterova

et al. 2021

Biomedicines

Self Cite

View full text Add to dashboard Cite

Treatment of acute respiratory distress syndrome (ARDS) is challenging due to its multifactorial aetiology. The benefit of antioxidant therapy was not consistently demonstrated by previous studies. We evaluated the effect of two different doses of intravenous (i.v.) N-acetylcysteine (NAC) on oxidative stress, inflammation and lung functions in the animal model of severe LPS-induced lung injury requiring mechanical ventilation. Adult Wistar rats with LPS (500 μg/kg; 2.2 mL/kg) were treated with i.v. NAC 10 mg/kg (NAC10) or 20 mg/kg (NAC20). Controls received saline. Lung functions, lung oedema, total white blood cell (WBC) count and neutrophils count in blood and bronchoalveolar lavage fluid, and tissue damage in homogenized lung were evaluated. NAC significantly improved ventilatory parameters and oxygenation, reduced lung oedema, WBC migration and alleviated oxidative stress and inflammation. NAC20 in comparison to NAC10 was more effective in reduction of oxidative damage of lipids and proteins, and inflammation almost to the baseline. In conclusion, LPS-instilled and mechanically ventilated rats may be a suitable model of ARDS to test the treatment effects at organ, systemic, cellular and molecular levels. The results together with literary data support the potential of NAC in ARDS.

show abstract

The Effect of Modified Porcine Surfactant Alone or in Combination with Polymyxin B on Lung Homeostasis in LPS-Challenged and Mechanically Ventilated Adult Rats

Cited by 5 publications

References 51 publications

Restoration of surfactant activity by polymyxin B in lipopolysaccharide-potentiated injury of immature rabbit lungs

Restoration of surfactant activity by polymyxin B in lipopolysaccharide-potentiated injury of immature rabbit lungs

Alveolar-Capillary Membrane-Related Pulmonary Cells as a Target in Endotoxin-Induced Acute Lung Injury

N-Acetylcysteine in Mechanically Ventilated Rats with Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome: The Effect of Intravenous Dose on Oxidative Damage and Inflammation

Contact Info

Product

Resources

About