Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0242706 (hyperoxia)
 5,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oxygen exposure for a sufficient duration at high partial pressure results in pulmonary edema in humans and animals. Although the specific mediators of oxygen toxicity are unknown, evidence suggests that oxygen-based radicals such as superoxide anion (O2.) are increased in the lungs in the presence of hyperoxia and contribute to this injury. A series of isomeric prostanoid compounds, the isoprostanes, are formed by the free radical-initiated lipid peroxidation of arachidonic acid (AA). One of these isomers, 8-iso-PGF2alpha, is elevated in the bronchial alveolar lavage fluid of rats exposed to 90% oxygen for 48 h and is associated with a significant increase in protein accumulation in the pulmonary extravascular space. Alveolar macrophages (AMs) are capable of producing large quantities of (O2.), suggesting a role in pulmonary oxygen toxicity. We hypothesized that isolated rat AMs exposed to hyperoxia generate increased amount of 8-iso-PGF2alpha. AMs were exposed to air or 90% oxygen for 6, 12, 24, 48, 72, 96, and 120 h in the absence and presence of AA and/or calcium ionophore (A23187) and 8-iso-PGF2alpha was measured in the culture media. Exposure of primary cultures of AMs to 90% oxygen resulted in a significant increase in 8-iso-PGF2alpha in the media (25 +/- 2 pg/mL) compared with air-exposed controls (14 +/- 1 pg/mL). The addition of 10 microM AA and 2 microM A23187 to the culture media resulted in a marked increase in 8-iso-PGF2alpha production by AMs exposed to air and 90% oxygen. However, treatment of AMs with the combination of AA and A23187, followed by exposure to 90% oxygen for 72 h, resulted in a 27-fold increase in 8-iso-PGF2alpha compared with media alone and 90% oxygen. AMs metabolized free and phospholipid-bound AA to 8-iso-PGF2alpha, an activity enhanced in the 90% oxygen environment. Finally, acetylsalicylic acid, a cyclooxygenase inhibitor and free radical scavenger, reduced but did not abolish production of 8-iso-PGF2alpha. This study provides evidence that AMs produce a free radical-mediated isomeric prostaglandin compound that may be involved in pulmonary oxygen toxicity.
 ...
PMID:8-ISO-PGF2alpha production by alveolar macrophages exposed to hyperoxia. 956 55

The aim of the present study is to investigate oxidative stress produced by experimental hypoxia and hyperoxia in young and old pampiniform plexus rats, in order to evaluate the oxidative role of oxygen. Oxidative stress causing molecular and cellular dysfunction increases in hypertension and can therefore be considered a state of oxidative stress. This consideration makes us reflect on the responsibility of oxidative stress in the veins of the pampiniform plexus, notoriously under high hydrostatic pressure. After experimental hypoxia and hyperoxia we studied the 8-iso-PGF2alpha release (a specific index of cellular oxidative stress) in young and old left pampiniform plexus rats. The basal 8-iso-PGF2alpha release showed a statistically significant difference P=0.0067 between young and old rats PP. After hypoxia and hyperoxia, the release was higher in young rats as compared to normoxia, respectively P=0.0001 and P=0.0002. After hypoxia the release was not modified in old rats P=0.544 while after hyperoxia the release was increased in old rats as compared to control P less than 0.0001. The results show how chronic hypoxia and hyperoxia represent two important causes of oxidative stress and lipid peroxidation in pampiniform plexus rats. In young rats an increase of oxidative stress suggests that pampiniform plexus is sensitive to variations of oxygen supply. In old rats the pampiniform plexus is liable to a reduction of oxygen-sensing mechanisms and it is possible that the missing oxidative answer to the hypoxia in old rats is attributable in all likelihood to adaptation to a hypoxic condition typical of aging.
 ...
PMID:Pampiniform plexus and oxidative stress during chronic hypoxia and hyperoxia. 1854 79

We examined the hypothesis that persistent pulmonary hypertension of the newborn (PPHN) associated with ibuprofen is due to alterations in biochemical and molecular regulators of oxidative stress and NO signaling. Newborn rats breathing 50% O2 or room air from the first day of life (P1), received early IP injections of: 1) indomethacin (0.2 mg/kg) on P1 and 0.1 mg/kg on P2 and P3; 2) ibuprofen (10 mg/kg) on P1 and 5 mg/kg on P2 and P3; or 3) saline on P1, P2 and P3, then euthanized on P4; or late treatment on P4, P5 and P6, then euthanized on P7. Lung biomarkers for oxidative stress (8- epi-PGF2a), DNA damage (8-hydroxy-2'-deoxyguanosine) and pulmonary hypertension (ET-1, big ET-1, and total NO) were assessed. Despite timing of the dose and oxygen exposure, both drugs resulted in increased alveolar size. Both drugs had no beneficial effects on oxidative stress. Indomethacin treatment in O2 resulted in higher pulmonary levels of 8-epi-PGF2alpha which was associated with downregulation of most antioxidant genes with early treatment and overexpression of GPX5 and 6 with late treatment. Early and late ibuprofen treatment suppressed hyperoxia-induced NOx production and downregulated iNOS. Postponing treatment had no significant beneficial effects on biomolecular regulators of oxidative stress and NO signaling. The effect of ibuprofen on pulmonary NOx may explain in part, the transient PPHN seen in ibuprofen-treated preterm infants.
 ...
PMID:Effects of combined hyperoxia and cyclooxygenase inhibition in neonatal rat lungs. 2058 71