8-epi-prostaglandin-f2alpha and Bronchopulmonary-Dysplasia

Our aim was to assess the plasma free 8-epi-prostaglandin F(2alpha) (8-isoprostane) and ascorbyl radical as risk indicators for oxidative damage in extremely low birth weight infants (ELBWIs) and the effect of N-acetylcysteine (NAC) on these markers. Plasma samples were collected on days 3 and 7 of life from infants who were enrolled in a randomized, controlled trial in which i.v. NAC or placebo was administered to ELBWIs during the first week of life, with the aim of preventing bronchopulmonary dysplasia (BPD). Plasma 8-isoprostane was analyzed in 83 infants using an enzyme immunoassay kit. Ascorbyl radical concentration was measured in 61 infants with electron spin resonance spectroscopy. The 8-isoprostane concentrations were similar in the NAC and placebo groups. In infants who later developed BPD or died (n = 29), the median (range) 8-isoprostane concentration was significantly higher (p = 0.001) on day 3 and day 7 [50.0 pg/mL (19-360) and 57.0 pg/mL (14-460), respectively] than in survivors without BPD [n = 54; 34.5 pg/mL (5-240) and 39.5 pg/mL (7-400), respectively]. The 8-isoprostane levels increased significantly more (p < 0.05) in infants who later developed periventricular leukomalacia. NAC treatment or the later development of BPD was not related to the ascorbyl radical levels. The ascorbyl radical level decreased significantly in all groups from day 3 to day 7, but the difference between the groups was not significant. The mean (SD) ascorbyl radical level on day 3 was significantly higher (p < 0.01) in infants who later developed periventricular leukomalacia [287 (124) versus 194 (90)]. These data suggest that plasma 8-isoprostane could serve as a marker in assessing the risk for BPD development in ELBWIs.

Topics: Biomarkers; Bronchopulmonary Dysplasia; Dehydroascorbic Acid; Dinoprost; Female; Humans; Infant, Newborn; Infant, Premature; Leukomalacia, Periventricular; Male; Oxidative Stress

Inflammation and oxidative stress play a key role in the development of bronchopulmonary dysplasia (BPD), possibly contributing to persistent respiratory morbidity after preterm birth. We aimed to assess if inflammatory markers were elevated in exhaled breath condensate (EBC) of infants born very prematurely (< 32 weeks gestation) at 12-16 corrected months of age, and if increased levels were associated with BPD diagnosis and respiratory morbidity.. EBC samples and respiratory questionnaires were collected from 15 term-born infants and 33 preterm-born infants, 12 with a neonatal BPD diagnosis. EBC samples were analysed for leukotriene B4 (inflammation) and 8-isoprostane (oxidative stress) concentrations using enzyme-linked immune-assays. Differences between groups were analysed by Kruskal-Wallis Test with post-hoc comparisons, independent samples t-test or Mann-Whitney U test depending on normality of the data.. Leukotriene B4 and 8-isoprostane levels were elevated in exhaled breath condensate of preterm-born infants compared to those born at term (mean difference [95% CI]; 1.52 [0.45, 2.59], p = 0.02; 0.77 [0.52, 1.02], p < 0.001, respectively). Leukotriene B4 and 8-isoprostane levels were independent of BPD diagnosis and respiratory morbidity over the first year of life.. Infants born very prematurely exhibit elevated markers of airway neutrophilic inflammation and oxidative stress beyond the first year of life, regardless of a neonatal diagnosis of chronic lung disease or respiratory morbidity during infancy. These findings may have implications for future lung health.. N/A.

Topics: Breath Tests; Bronchopulmonary Dysplasia; Female; Humans; Infant; Infant, Newborn; Infant, Premature; Inflammation; Leukotriene B4; Premature Birth

Prematurity and its main respiratory complication, bronchopulmonary dysplasia (BPD), are potentially associated with lifelong respiratory morbidities and/or lung function abnormalities. The mechanisms behind these long-term respiratory problems are still unclear. We assessed airway oxidative stress in adolescents born very pre-term (≤ 32 gestational weeks) by measuring 8-isoprostane concentration in exhaled breath condensate (EBC). In addition, the study protocol included spirometry and measurement of exhaled nitric oxide fraction (F(eNO)). The study groups included 34 ex-pre-term adolescents with BPD, 18 ex-pre-term adolescents without BPD and 34 healthy controls born at term. Regardless of a history of BPD, the ex-premature adolescents had higher EBC 8-isoprostane levels (median (interquartile range) BPD 9.5 (7.3-12.2) pg·mL(-1); pre-term non-BPD 10 (8.1-16) pg·mL(-1)) than the controls (3.2 (1.9-6.5) pg·mL(-1)) (p<0.001). Forced expiratory volume in 1 s was lower in the BPD group (mean ± sd Z-score -2.1 ± 1.58) than in the pre-term non-BPD individuals (-1.13 ± 1.15), who showed in turn significantly lower values than the controls (0.18 ± 0.83; p<0.001). F(eNO) was similar in the three groups (p=0.55). Our data show that, after premature birth, evidence of oxidative stress in the airways may be detected into adolescence, suggesting that long-term respiratory abnormalities after pre-term birth may be associated with an ongoing airway disease and not just a stabilised structural lung damage.

Topics: Adolescent; Biomarkers; Breath Tests; Bronchopulmonary Dysplasia; Dinoprost; Female; Humans; Infant, Newborn; Infant, Premature; Male; Oxidative Stress; Respiratory System

Oxygen toxicity is thought to contribute to the development of bronchopulmonary dysplasia (BPD). Oxidant injury leads to formation of F(2)-isoprostanes (F(2)-IsoP). We hypothesized that urinary excretion of the stable metabolite of F(2)-IsoP, 8-iso-PGF(2alpha), would be higher in infants who develop BPD than those who did not.. Forty infants <30-weeks gestational age (GA) were enrolled, 24 infants with BPD and 16 without BPD. Urine specimens were collected weekly and stored at -80 degrees C until analyzed. Urinary 8-iso-PGF(2alpha) was measured by gas chromatography/mass spectrometry (GC-MS) and normalized to creatinine excretion.. GA and birth weight (BW) were lower in infants who developed BPD than those who did not. Urinary 8-iso-PGF(2alpha) levels in the first or third weeks of age were not significantly different between the two groups.. Urinary excretion of 8-iso-PGF(2alpha) in early postnatal life in preterm infants is not correlated with the development of BPD.

Topics: Biomarkers; Birth Weight; Bronchopulmonary Dysplasia; Dinoprost; F2-Isoprostanes; Female; Gas Chromatography-Mass Spectrometry; Humans; Infant, Newborn; Infant, Very Low Birth Weight; Male; Predictive Value of Tests; Prognosis; Risk Factors

Newborn rats exposed to 60% O(2) for 14 d demonstrated a bronchopulmonary dysplasia-like lung morphology and pulmonary hypertension. A 21-aminosteroid antioxidant, U74389G, attenuated both pulmonary hypertension and macrophage accumulation in the O(2)-exposed lungs. To determine whether macrophage accumulation played an essential role in the development of pulmonary hypertension in this model, pups were treated with gadolinium chloride (GdCl(3)) to reduce lung macrophage content. Treatment of 60% O(2)-exposed animals with GdCl(3) prevented right ventricular hypertrophy (p < 0.05) and smooth muscle hyperplasia around pulmonary vessels, but had no effect on morphologic changes in the lung parenchyma. In addition, GdCl(3) inhibited 60% O(2)-mediated increases in endothelin-1, 8-isoprostane, and nitrotyrosine residues. Organotypic cultures of fetal rat distal lung cells were subjected to cyclical mechanical strain to assess the potential role of GdCl(3)-induced blockade of stretch-mediated cation channels in these effects. Mechanical strain caused a moderate increase of endothelin-1 (p < 0.05), which was unaffected by GdCl(3), but had no effect on 8-isoprostane or nitric oxide synthesis. A critical role for endothelin-1 in O(2)-mediated pulmonary hypertension was confirmed using the combined endothelin receptor antagonist SB217242. We concluded that pulmonary macrophage accumulation, in response to 60% O(2), mediated pulmonary hypertension through up-regulation of endothelin-1.

Topics: Animals; Animals, Newborn; Bronchopulmonary Dysplasia; Cell Movement; Cells, Cultured; Dinoprost; Endothelin-1; F2-Isoprostanes; Gadolinium; Humans; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Infant, Newborn; Macrophages, Alveolar; Oxygen; Rats; Rats, Sprague-Dawley; Tyrosine