Isoprostane levels in urine of preterm newborns treated with ibuprofen for patent ductus arteriosus closure

Abstract

Patent ductus arteriosus (PDA) is the most common cardiovascular abnormality of the preterm infant usually treated with ibuprofen (IBU). PDA is strictly related to oxidative stress (OS) in neonates. This study tests the hypothesis that OS occurs in neonates with PDA and that IBU treatment reduces OS. Forty-three preterm babies with gestational age (GA) <33 weeks were studied prospectively. Three urine samples were collected: at time 0 (before starting treatment), time 1 (after pharmacological PDA closure), and time 2 (7 days after the end of treatment) in all patients. OS was studied by measuring urinary isoprostane (IPs) levels. The results showed significant changes in urinary IP levels from time 0 to time 2 (Kruskal-Wallis, p=0.047). Time trend showed a significant decrease in IPs from time 0 to time 1 after IBU therapy (p=0.0067). This decrease was followed by an increase in IPs levels 7 days after treatment. IBU therapy for PDA closure reduced the risk of OS related to free-radical (FR) generation. This antioxidant effect of IBU may be beneficial in preterm babies with PDA who are at high risk for OS.

Antioxidants and Biomarkers of Oxidative Stress in Preterm Infants with Symptomatic Patent Ductus Arteriosus

“…34 Low levels of 8-isoPGF 2α are of particular significance because the observation may reflect immature O 2 sensing and signaling of the DA of preterm infants and may suggest the predictive value of low 8-isoPGF 2α as a biomarker for hsPDA. Higher level of 8-isoPGF 2α posttreatment is most likely due to increased oxygenation and ROS levels and confirms previous findings of increased isoprostane postibuprofen treatment as shown by Longini et al 39 However, we cannot rule out the possibility that inhibition of cyclooxygenase (COX) (by pharmacologic treatment of PDA) may have driven AA toward the nonenzymatic pathway and caused elevation of 8-isoPGF 2α .…”

Isoprostanes as physiological mediators of transition to newborn life: novel mechanisms regulating patency of the term and preterm ductus arteriosus

“…Oxidative stress is also increased during premature birth (3,5,7) or complicated pregnancies (2,4,25,26) and in various neonatal pathologies, including retinopathy of prematurity, bronchopulmonary dysplasia, hypoxic–ischemic encephalopathy, periventricular leukomalacia, intrauterine growth restriction, and hemolysis (2,3,27). Recent studies also show that delayed closure of the DA after birth leaves the newborn at risk for disorders that are associated with oxidative stress (12), and that premature infants with PDA have increased isoprostane levels that decline with treatment (28). Most of these studies were correlative and based on associations with increased levels of plasma or urine 8-iso-PGF2α.…”

Resuscitating preterm infants with 100% oxygen is associated with higher oxidative stress than room air

“…External calibration points were prepared by adding to 200-lL aliquot of water 10 lL of the working solutions of F2-IsoP with the concentrations ranging from 0.25 up to 25 ng/mL in order to obtain resulting aqueous solutions from 12.5 up to 1250 pg/mL (15,17,18). Firstly, filtration was performed with a 100-kDa molecular weight cut-off Whatman ultracentrifuge filter followed by filtration with a filter set at a 20-kDa cut-off.…”

“…A clear extract was obtained by a further centrifugation, and the final injection of 100 lL represented 25 lL of the original specimen. External calibration points were prepared by adding to 200-lL aliquot of water 10 lL of the working solutions of F2-IsoP with the concentrations ranging from 0.25 up to 25 ng/mL in order to obtain resulting aqueous solutions from 12.5 up to 1250 pg/mL (15,17,18). Changes, such as an increase or a decrease, between the two time-points, two and 12 hours, for AOPP, NPBI and IsoP, were considered to evaluate the increase in oxidative stress biomarkers few hours after birth.…”