2 research outputs found
Effects of a superoxide dismutase mimetic on biomarkers of lung angiogenesis and alveolarization during hyperoxia with intermittent hypoxia
Extremely premature neonates requiring oxygen therapy develop an accumulation of reactive oxygen species (ROS), impaired alveolarization and dysmorphic pulmonary vasculature. Regulators of ROS (i.e. antioxidants), alveolarization (i.e. matrix metalloproteinases - MMPs) and microvascular maturation (i.e. vascular endothelial growth factor - VEGF) are altered in bronchopulmonary dysplasia (BPD). We tested the hypothesis that early treatment with MnTBAP, a superoxide dismutase mimetic and superoxide anion and peroxynitrite scavenger, alters lung biomarkers of angiogenesis and alveolarization during hyperoxia with intermittent hypoxia (IH) in neonatal rats. Neonatal rats were exposed to 50% O2 with brief IH episodes (12% O2) from P0 to P14, or to room air (RA). On P0, P1 & P2, the pups received a daily IP injection of 1, 5, or 10 mg/kg MnTBAP, or saline. At P14, the pups were either euthanized, or allowed to recover in RA until P21. RA littermates were similarly treated. Lung VEGF, sVEGFR-1, MMP-2, MMP-9 and TIMP-1 were determined. Low-dose MnTBAP (1 mg/kg) prevented the increase in lung VEGF induced by intermittent hypoxia noted in the control group. This dose was also effective for decreasing MMP-9 and MMP-9/TIMP-1 ratio suggesting an anti-inflammatory effect for MnTBAP. IH decreased MMP-2 with no ameliorating effect by MnTBAP. Our data demonstrate that brief, repeated intermittent hypoxia during hyperoxia can alter biomarkers responsible for normal microvascular and alveolar development. In addition to prevention of hypoxic events, the use of antioxidants needs to be explored as a possible therapeutic intervention in neonates at risk for the development of oxidative lung injury
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Combined antenatal and postnatal steroid effects on fetal and postnatal growth, and neurological outcomes in neonatal rats.
Preterm infants are often exposed to both antenatal and postnatal glucocorticoids (GCs). We tested the hypothesis that combined antenatal and postnatal GCs have long-lasting adverse effects on fetal and neonatal growth, growth factors, and neurological outcomes. Pregnant rats were administered a single IM dose of betamethasone (0.2 mg/Kg, AB), dexamethasone (0.2 mg/Kg, AD), or equivalent volumes of saline (AS) at 17 & 18 days gestation. Following delivery, pups from each treatment group were sacrificed at P0, and the remainder was treated with a single IM dose of either betamethasone (0.25 mg/Kg, PB), dexamethasone (0.25 mg/Kg, PD), or equivalent volumes of saline (PS) on P5, P6, and P7. Somatic growth, neurological status, and growth factors were determined at P14, P21, and P45. At birth, AD resulted in decreased somatic growth. AB advanced the hopping reflex associated with spinal rhythmic mechanisms. At P21, all GC groups were growth suppressed, but only the AS/PD group had deficits in brain weight and delayed plantar reflex associated with brainstem function. By P45, sustained reductions in body and brain weight occurred all combined antenatal and postnatal GC groups, as well as elevated ACTH and corticosterone. Retardation in plantar reflex occurred in all AD groups. IGF-I, GH and insulin levels were elevated at all ages with dexamethasone. Combined antenatal and postnatal GCs has persistent detrimental lasting effects on growth, growth factors, neurological outcomes, and HPA axis activity. Whether these effects persist in adult life and are risk factors for insulin resistance, remains to be elucidated