scholarly journals Recombinant Human Superoxide Dismutase and N-Acetylcysteine Addition to Exogenous Surfactant in the Treatment of Meconium Aspiration Syndrome

Molecules ◽  
2019 ◽  
Vol 24 (5) ◽  
pp. 905 ◽  
Author(s):  
Jana Kopincova ◽  
Maros Kolomaznik ◽  
Pavol Mikolka ◽  
Petra Kosutova ◽  
Juliana Topercerova ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Efficiency Index ◽  
Meconium Aspiration Syndrome ◽  
Mitogen Activated Protein Kinase ◽  
Exogenous Surfactant ◽  
Duration Of Treatment ◽  
Pulmonary Tissue ◽  
Meconium Aspiration ◽  
Oxidative Markers ◽  
Mitogen Activated Protein

This study aimed to evaluate the molecular background of N-acetylcysteine (NAC) and recombinant human superoxide dismutase (rhSOD) antioxidant action when combined with exogenous surfactant in the treatment of meconium aspiration syndrome (MAS), considering redox signalling a principal part of cell response to meconium. Young New Zealand rabbits were instilled with meconium suspension (Mec) and treated by surfactant alone (Surf) or surfactant in combination with i.v. NAC (Surf + NAC) or i.t. rhSOD (Surf + SOD), and oxygen-ventilated for 5 h. Dynamic lung-thorax compliance, mean airway pressure, PaO2/FiO2 and ventilation efficiency index were evaluated every hour; post mortem, inflammatory and oxidative markers (advanced oxidation protein products, total antioxidant capacity, hydroxynonenal (HNE), p38 mitogen activated protein kinase, caspase 3, thromboxane, endothelin-1 and secretory phospholipase A2) were assessed in pulmonary tissue homogenates. rhSOD addition to surfactant improved significantly, but transiently, gas exchange and reduced levels of inflammatory and oxidative molecules with higher impact; Surf + NAC had stronger effect only on HNE formation, and duration of treatment efficacy in respiratory parameters. In both antioxidants, it seems that targeting reactive oxygen species may be strong supporting factor in surfactant treatment of MAS due to redox sensitivity of many intracellular pathways triggered by meconium.

scholarly journals Lung Inflammatory and Oxidative Alterations After Exogenous Surfactant Therapy Fortified With Budesonide in Rabbit Model of Meconium Aspiration Syndrome

2016 ◽  
pp. S653-S662 ◽  
Author(s):  
P. MIKOLKA ◽  
J. KOPINCOVÁ ◽  
P. KOŠÚTOVÁ ◽  
D. ČIERNY ◽  
A. ČALKOVSKÁ ◽  
...  
Keyword(s):  
Oxidative Damage ◽  
Expression Profiles ◽  
Rabbit Model ◽  
Weight Ratio ◽  
Meconium Aspiration Syndrome ◽  
Exogenous Surfactant ◽  
Lung Edema ◽  
Edema Formation ◽  
Meconium Aspiration ◽  
Cell Counts

Meconium aspiration syndrome (MAS) triggers inflammatory and oxidative pathways which can inactivate both pulmonary surfactant and therapeutically given exogenous surfactant. Glucocorticoid budesonide added to exogenous surfactant can inhibit inflammation and thereby enhance treatment efficacy. Neonatal meconium (25 mg/ml, 4 ml/kg) was administered intratracheally (i.t.) to rabbits. When the MAS model was prepared, animals were treated with budesonide i.t. (Pulmicort, 0.25 mg/kg, M+B); with surfactant lung lavage (Curosurf®, 10 ml/kg, 5 mg phospholipids/ml, M+S) followed by undiluted Curosurf® i.t. (100 mg phospholipids/kg); with combination of budesonide and surfactant (M+S+B); or were untreated (M); or served as controls with saline i.t. instead of meconium (C). Animals were oxygen-ventilated for additional 5 h. Cell counts in the blood and bronchoalveolar lavage fluid (BAL), lung edema formation (wet/dry weight ratio), oxidative damage of lipids/ proteins and inflammatory expression profiles (IL-2, IL-6, IL-13, TNF-α) in the lung homogenate and plasma were determined. Combined surfactant+budesonide therapy was the most effective in reduction of neutrophil counts in BAL, oxidative damage, levels and mRNA expression of cytokines in the lung, and lung edema formation compared to untreated animals. Curosurf fortified with budesonide mitigated lung inflammation and oxidative modifications what indicate the perspectives of this treatment combination for MAS therapy.

POLYETHYLENE GLYCOL ADDITION DOES NOT IMPROVE EXOGENOUS SURFACTANT FUNCTION IN AN EXPERIMENTAL MODEL OF MECONIUM ASPIRATION SYNDROME

2009 ◽  
Vol 35 (1) ◽  
pp. 76-88 ◽  
Author(s):  
Joao Cesar Lyra ◽  
Renata Suman Mascaretti ◽  
Alexander Roberto Precioso ◽  
Luciana Branco Haddad ◽  
Thais Mauad ◽  
...  
Keyword(s):  
Polyethylene Glycol ◽  
Experimental Model ◽  
Meconium Aspiration Syndrome ◽  
Exogenous Surfactant ◽  
Meconium Aspiration

Modified porcine surfactant enriched by recombinant human superoxide dismutase for experimental meconium aspiration syndrome

Life Sciences ◽  
2018 ◽  
Vol 203 ◽  
pp. 121-128 ◽  
Author(s):  
Jana Kopincova ◽  
Pavol Mikolka ◽  
Maros Kolomaznik ◽  
Petra Kosutova ◽  
Andrea Calkovska ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Meconium Aspiration Syndrome ◽  
Meconium Aspiration

scholarly journals N-Acetylcysteine Advancement of Surfactant Therapy in Experimental Meconium Aspiration Syndrome: Possible Mechanisms

2014 ◽  
pp. S629-S642 ◽  
Author(s):  
J. KOPINCOVÁ ◽  
D. MOKRÁ ◽  
P. MIKOLKA ◽  
M. KOLOMAZNÍK ◽  
A. ČALKOVSKÁ
Keyword(s):  
Oxidative Damage ◽  
Therapeutic Effect ◽  
Neutrophil Migration ◽  
Oxygenation Index ◽  
Meconium Aspiration Syndrome ◽  
Surfactant Therapy ◽  
Total Leukocyte Count ◽  
Exogenous Surfactant ◽  
Meconium Aspiration ◽  
Respiratory Parameters

Meconium aspiration syndrome (MAS) is meconium-induced respiratory failure of newborns associated with activation of inflammatory and oxidative pathways. For severe MAS, exogenous surfactant treatment is used which improves respiratory functions but does not treat the inflammation. Oxidative process can lead to later surfactant inactivation; hence, surfactant combination with antioxidative agent may enhance the therapeutic effect. Young New Zealand rabbits were instilled by meconium suspension and treated by surfactant alone, N-acetylcysteine (NAC) alone or by their combination and oxygen-ventilated for 5 h. Blood samples were taken before and 30 min after meconium application and 30 min, 1, 3 and 5 h after the treatment for evaluating of oxidative damage, total leukocyte count, leukocyte differential count and respiratory parameters. Leukocyte differential was assessed also in bronchoalveolar lavage fluid. NAC alone had only mild therapeutic effect on MAS. However, the combination of NAC and surfactant facilitated rapid onset of therapeutic effect in respiratory parameters (oxygenation index, PaO2/FiO2) compared to surfactant alone and was the only treatment which prevented neutrophil migration into the lungs, oxidative damage and lung edema. Moreover, NAC suppressed IL-8 and IL-β formation and thus seems to be favorable agent for improving surfactant therapy in MAS.

Airway lavage with exogenous surfactant in an animal model of meconium aspiration syndrome

2005 ◽  
Vol 47 (3) ◽  
pp. 237-241 ◽  
Author(s):  
Erquan Zhang ◽  
Takehiko Hiroma ◽  
Takeshi Sahashi ◽  
Atsuko Taki ◽  
Tatsuya Yoda ◽  
...  
Keyword(s):  
Animal Model ◽  
Meconium Aspiration Syndrome ◽  
Exogenous Surfactant ◽  
Meconium Aspiration

Exogenous surfactant improves lung compliance and oxygenation in adult rats with meconium aspiration

1994 ◽  
Vol 77 (4) ◽  
pp. 1961-1971 ◽  
Author(s):  
B. Sun ◽  
E. Herting ◽  
T. Curstedt ◽  
B. Robertson
Keyword(s):  
Lavage Fluid ◽  
Saline Group ◽  
Meconium Aspiration Syndrome ◽  
Lung Compliance ◽  
Exogenous Surfactant ◽  
High Dose ◽  
Adult Rats ◽  
Meconium Aspiration ◽  
Adult Rat ◽  
Arterial Po2

We studied the effects of exogenous surfactant on lung function and morphology in an adult rat model of severe meconium aspiration syndrome. Animals ventilated with 100% oxygen received 4–6 ml of human meconium (25 mg/ml) intratracheally. After 30 min, lung-thorax compliance had decreased by > 30% and arterial PO2 was < 10 kPa. Animals were then treated with no material (MECO group), 0.9% NaCl (MECO-saline group), natural porcine surfactant (NPS group) at a dose of 100 mg/kg, or modified porcine surfactant at a dose of either 100 (MPS100 group) or 200 mg/kg (MPS200 group) and were ventilated for another 180 min. Immediate and sustained improvement of arterial PO2 and compliance was observed in the MPS200 group, whereas the MPS100 and NPS groups showed less pronounced effects. There was a significant improvement of quasi-static lung volumes at maximum insufflation pressure and during deflation in the MPS200, MPS100, and NPS groups. Recordings with Wilhelmy balance showed that minimum surface tension of bronchoalveolar lavage fluid from animals receiving either type or dose of surfactant was significantly lower than in the MECO and MECO-saline groups. Meconium aspiration induced diffuse and prominent atelectasis, intra-alveolar edema, and hyaline membranes. These morphological abnormalities were reversed by exogenous surfactant, especially by the high-dose regimen.

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