Abstract
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.
Highlights
Meconium aspiration syndrome (MAS) is a serious respiratory failure of newborns caused by aspiration of meconium-stained amniotic fluid (MSAF) before or during delivery, recently assigned to neonatal acute respiratory distress syndrome (ARDS) [1]
When we compared the effect of recombinant human superoxide dismutase (rhSOD) combined with surfactant with NAC combined with surfactant from the previous experiments, we found some differences in these two antioxidants
Four of seven animals were used in this experiment: group instilled with meconium without anyFour treatment group); group meconiumgroup with surfactant-only treatment groups (Mec of seven animals wereinstilled used in with this experiment: instilled with meconium (Surf group); group instilled with meconium with combined surfactant and treatment without any treatment (Mec group); group instilled with meconium with surfactant-only treatment group); group meconium combined surfactant and NAC
Summary
Meconium aspiration syndrome (MAS) is a serious respiratory failure of newborns caused by aspiration of meconium-stained amniotic fluid (MSAF) before or during delivery, recently assigned to neonatal acute respiratory distress syndrome (ARDS) [1]. Medical intervention to oxidant/antioxidant balance had been tried in numerous pulmonary diseases for many years [5,6,7,8,9] As it was pointed out by Greenwald in a critical review, antioxidant therapy makes true sense only in those situations “where oxygen radicals can be truly expected to play a role based on what we know about their biochemistry and pathology” [10]. In serious MAS, high fractions of oxygen are often needed to maintain sufficient oxygenation of newborns during ventilatory support, which leads to ROS overproduction, so direct oxidative impairment to biomolecules together with ROS-mediated signalling pathways play important roles in meconium-induced lung injury and injury of the other organs [12,14], and antioxidant therapy in MAS is worthwhile
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