The Anti-Inflammatory Agent N-Acetyl Cysteine Exacerbates Endotoxin-Induced Hypoxemia and Hypotension and Induces Polycythemia in the Ovine Fetus

Probyn, Megan Elizabeth; Cock, Megan L.; Duncan, Jhodie R.; Tolcos, Mary; Hale, Nadia; Shields, Amy; Rees, Sandra; Harding, Richard

doi:10.1159/000280385

Cited by 16 publications

(12 citation statements)

References 70 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The beneficial effect of NAC could therefore be in part depends on this property. Although it has been reported evidence of NAC-induced vasodilation and hypotension [39,40], we didn’t found any systemic effect of NAC in our study.…”

Section: Discussioncontrasting

confidence: 80%

N-acetylcysteine improves established monocrotaline-induced pulmonary hypertension in rats

et al. 2014

View full text Add to dashboard Cite

BackgroundThe outcome of patients suffering from pulmonary arterial hypertension (PAH) are predominantly determined by the response of the right ventricle to the increase afterload secondary to high vascular pulmonary resistance. However, little is known about the effects of the current available or experimental PAH treatments on the heart. Recently, inflammation has been implicated in the pathophysiology of PAH. N-acetylcysteine (NAC), a well-known safe anti-oxidant drug, has immuno-modulatory and cardioprotective properties. We therefore hypothesized that NAC could reduce the severity of pulmonary hypertension (PH) in rats exposed to monocrotaline (MCT), lowering inflammation and preserving pulmonary vascular system and right heart function.MethodsSaline-treated control, MCT-exposed, MCT-exposed and NAC treated rats (day 14–28) were evaluated at day 28 following MCT for hemodynamic parameters (right ventricular systolic pressure, mean pulmonary arterial pressure and cardiac output), right ventricular hypertrophy, pulmonary vascular morphometry, lung inflammatory cells immunohistochemistry (monocyte/macrophages and dendritic cells), IL-6 expression, cardiomyocyte hypertrophy and cardiac fibrosis.ResultsThe treatment with NAC significantly decreased pulmonary vascular remodeling, lung inflammation, and improved total pulmonary resistance (from 0.71 ± 0.05 for MCT group to 0.50 ± 0.06 for MCT + NAC group, p < 0.05). Right ventricular function was also improved with NAC treatment associated with a significant decrease in cardiomyocyte hypertrophy (625 ± 69 vs. 439 ± 21 μm2 for MCT and MCT + NAC group respectively, p < 0.001) and heart fibrosis (14.1 ± 0.8 vs. 8.8 ± 0.1% for MCT and MCT + NAC group respectively, p < 0.001).ConclusionsThrough its immuno-modulatory and cardioprotective properties, NAC has beneficial effect on pulmonary vascular and right heart function in experimental PH.

show abstract

Section: Discussioncontrasting

confidence: 80%

N-acetylcysteine improves established monocrotaline-induced pulmonary hypertension in rats

et al. 2014

View full text Add to dashboard Cite

show abstract

“…2a–c), which is supported by other reports showing that NAC improved survival of offspring after LPS injection in rat dams at GD16-183651, provided protection against fetal death and preterm labor induced by maternal inflammation33, and lowered the inflammatory cytokine response in amniotic fluid and placenta in rats3537. A previous publication reported that NAC has potential life-threatening effects on a fetus that has been exposed to endotoxins, which worsens LPS-induced fetal hypoxemia and hypotension52. However, our data show no reduction of hemoglobin and erythrocyte levels when NAC is administered (Table 1).…”

Section: Discussionsupporting

confidence: 66%

N-acetylcysteine attenuates lipopolysaccharide-induced impairment in lamination of Ctip2-and Tbr1- expressing cortical neurons in the developing rat fetal brain

Chao

Chen

Yang

et al. 2016

Sci Rep

View full text Add to dashboard Cite

Oxidative stress and inflammatory insults are the major instigating events of bacterial intrauterine infection that lead to fetal brain injury. The purpose of this study is to investigate the remedial effects of N-acetyl-cysteine (NAC) for inflammation-caused deficits in brain development. We found that lipopolysaccharide (LPS) induced reactive oxygen species (ROS) production by RAW264.7 cells. Macrophage-conditioned medium caused noticeable cortical cell damage, specifically in cortical neurons. LPS at 25 μg/kg caused more than 75% fetal loss in rats. An increase in fetal cortical thickness was noted in the LPS-treated group. In the enlarged fetal cortex, laminar positioning of the early born cortical cells expressing Tbr1 and Ctip2 was disrupted, with a scattered distribution. The effect was similar, but minor, in later born Satb2-expressing cortical cells. NAC protected against LPS-induced neuron toxicity in vitro and counteracted pregnancy loss and alterations in thickness and lamination of the neocortex in vivo. Fetal loss and abnormal fetal brain development were due to LPS-induced ROS production. NAC is an effective protective agent against LPS-induced damage. This finding highlights the key therapeutic impact of NAC in LPS-caused abnormal neuronal laminar distribution during brain development.

show abstract

“…127 However, there are some concerns that N-acetylcysteine may compromise fetal cardiovascular stability and to date, no large clinical trials have evaluated systemic N-acetylcysteine administration in newborn infants - or their mothers - prior to delivery. 128 …”

Section: Potential Future Interventions To Reduce Bacteraemia-associamentioning

confidence: 99%

Infection-induced inflammation and cerebral injury in preterm infants

Strunk

Inder

Wang

et al. 2014

The Lancet Infectious Diseases

246

219

View full text Add to dashboard Cite

Summary Preterm birth and infectious diseases are the most common causes of neonatal and early childhood deaths worldwide. The rates of preterm birth have increased over recent decades and currently account for 11% of all births globally. Preterm infants are at significant risk of severe infection in early life and throughout childhood. Bacteraemia and/or inflammation during the neonatal period in preterm infants is associated with adverse outcomes, including death, chronic lung disease and neurodevelopmental impairment. Recent studies suggest that bacteraemia may trigger cerebral injury even without penetration of viable bacteria into the central nervous system. Here we review available evidence that supports the concept of a strong association between bacteraemia, inflammation and cerebral injury in preterm infants, with an emphasis on the underlying biological mechanisms, clinical correlates and translational opportunities.

show abstract

The Anti-Inflammatory Agent N-Acetyl Cysteine Exacerbates Endotoxin-Induced Hypoxemia and Hypotension and Induces Polycythemia in the Ovine Fetus

Cited by 16 publications

References 70 publications

N-acetylcysteine improves established monocrotaline-induced pulmonary hypertension in rats

N-acetylcysteine improves established monocrotaline-induced pulmonary hypertension in rats

N-acetylcysteine attenuates lipopolysaccharide-induced impairment in lamination of Ctip2-and Tbr1- expressing cortical neurons in the developing rat fetal brain

Infection-induced inflammation and cerebral injury in preterm infants

Contact Info

Product

Resources

About