N-Acetylcysteine Amide Exerts Possible Neuroprotective Effects in Newborn Pigs after Perinatal Asphyxia.
Neonatology
; 111(1): 12-21, 2017.
Article
in En
| MEDLINE
| ID: mdl-27497671
ABSTRACT
BACKGROUND:
Perinatal asphyxia and ensuing reoxygenation change the antioxidant capacity of cells and organs.OBJECTIVES:
To analyze the neuroprotective effect of the antioxidant N-acetylcysteine amide (NACA) after perinatal hypoxia-reoxygenation with an emphasis on proinflammatory cytokines and the transcription factor NF-κB in the prefrontal cortex of neonatal pigs.METHODS:
Twenty-nine newborn pigs, aged 12-36 h, were subjected to global hypoxia and hypercapnia. One sham-operated group (n = 5) and 2 experimental groups (n = 12) were exposed to 8% oxygen, until the base excess was -20 mmol/l or the mean arterial blood pressure fell to <20 mm Hg (asphyxia with NACA or saline). The pigs were observed for 9.5 h after hypoxia. Samples of prefrontal cortex and plasma were analyzed.RESULTS:
Cortex there was no significant difference in mRNA expression between the intervention groups regarding IL-1ß, IL6, TNFα, MMP2, MMP9 or IL18. Pigs exposed to hypoxia-reoxygenation and treatment with NACA (NACA-pigs) had a significantly lower protein concentration of IL-1ß than pigs treated with saline (placebo controls), i.e. 8.8 ± 3.9 versus 16.8 ± 10.5 pg/mg protein (p = 0.02). The activation of the transcription factor NF-κB (measured as the fold-change of phosphorylated p65Ser 536), was reduced in the NACA-pigs when compared to the placebo controls (5.2 ± 4.3 vs. 16.0 ± 13.5; p = 0.02). No difference between the intervention groups regarding brain histopathology or in the levels of 8-oxoguanine measured in the prefrontal cortex were observed. Plasma the NACA-pigs had a stronger reduction of TNFα in the first 30 min following asphyxia compared with the placebo controls, i.e. 36 (30-44) versus 24 (14-32)% (p = 0.01).CONCLUSION:
The reduced levels of the pivotal inflammatory markers IL-1ß and TNFα and the transcription factor NF-κB may indicate that NACA has possible neuroprotective effects after perinatal asphyxia.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Oxygen
/
Acetylcysteine
/
Asphyxia Neonatorum
/
Neuroprotective Agents
/
Hypoxia
Limits:
Animals
Language:
En
Journal:
Neonatology
Journal subject:
PERINATOLOGIA
Year:
2017
Document type:
Article
Affiliation country:
Noruega