Hyperoxic Injury of Immature Guinea Pig Lung Is Mediated via Hydroxyl Radicals

Abstract

Curdiovnsculal-Re,rearch, T h R a y n~Suppnrt of preterm infants with ventilation and oxygen therapy frequently leads to Lhe development of chronic lung disease. Oxidative stress, rhmugh the generation of excess oxygen free radicals, is thought to play a major role in this condition. At present the radical species responsible for oxidative lung ~n j u r y is not known, and cKcctive antioxidant based therapies are not available. The purposc of this study was to determine whether hydroxyl rad~cals, potent reactive oxygen species, are ~nvolved in chronic oxidative lung injury. To obtain this information we developed a animal model of chronic lung injury using the pretcrm guinea pig and analyzed lung tissuc from these pups for o-tyrosine, a specific marker of hydroxyl radical attack. In normoxia control pups the pulmonary content of n-tyrosine was low during the first 4 wk of life (range 0.1 1-0.12% tyrosine). Pups Thc role of oxygen in the development of neonatal Iung disease is unequivocal (1). Since the initial pmposal by Gerschman et al.(Z), the evidencc implicating oxygen free radicals in hyperoxiainduced lung injury has increased steadily. In 1981 Freeman and Ctapo (3) demonstrated that hypcroxic-exposure resulted in increased oxygen radical production jn rat lungs. These investigators subsequently showed that augmentation of superoxide disrnutase in endotheljal cells prt?vented oxidative injury, implicating superoxide anions in the injury p r m s (4). These findings were examined in newborn infants with lung disease, and supcroxide dismutase was found to provide some benefit (5), reinforcing the free radical hypothesis but without providing any further information as to which radicals were involved. Pitkaenen et 01. (6) added further weight to this hypothesis when they reported increased ethane and pentane levels in expired air of ventilated neonates. Schlenzig er 01, (7) also reported increased urinary excretion of malondialdchyde in ventilated premature infants which corsetated with FiOz levcls. None of the above clinical studies provided information regarding the oxygen free radical species involved in neonatal lung injury. Indeed, similar studies in maintained in 85% oxygen were found to have increasing rung a-tyrosine over this period (d METHODSAnimals. Virgin, female Hartley strain guinea pigs (500 g) obtained horn our colony west caged in pairs in a room

Transcription and activity of antioxidant enzymes after ionizing irradiation in radiation-resistant and radiation-sensitive mice

“…The determination of otyrosine was carried out after acid hydrolysis of liver samples by an HPLC method given in a previous paper (31,32). Briefly, The hydrolysates were evaporated to dryness on a Pierce Reactitherme at 60°C and redissolved in distilled water.…”

On the pulmonary toxicity of oxygen: III. The induction of oxygen dependency by oxygen use

“…Claireaux (1975) summarized much of the earlier work. Other pertinent reports are those of Ambrus, et al (1968), , Frank et al (1977), Frank et al (1978), Mortola (1983), Fisher et al (1991), Langley and Kelly (1994), Kelly and Lubec (1995), Phillips et al (1995), Han, et al (1996), Schock et al (2001), Collard et al (2004), and Higgins et al (2007). One paper stands out from the earlier work on these issues by the authors' clear conclusion that the oxygen was more of a problem than the ventilatory measures used (Nash et al, 1967).…”

“…The term oxygen toxicity is in common use (Turrens at al, 1984;Nishiki et al, 1976) but so also are alternative phrases such as hyperoxic injury (Kelly and Lubec, 1995), oxygen-induced lung injury (Ambrus et al, 1968;Phillips et al, 1995), oxidative damage (Collard et al, 2004), and oxidative stress (Schock et al, 2001), inter alia. The important paper by Claireaux (1975) used the neutral phrase, the effect of oxygen on the lung, in the context of what he termed the exudative phase of oxygen toxicity.…”

Lung Diseases - Selected State of the Art Reviews

“…Therefore, high oxygen supplementation coupled with low SOD activity add to oxidative stress, and this may be evidenced by an increase in the by-products of lipid peroxidation (lipid peroxides, malondialdehyde, HNE, alkanes such as ethane and pentane, and isoprostanes) and/or of protein oxidation (carbonyl compounds, o-dityrosine). Newborn infants receiving O 2 supplementation have demonstrably elevated levels of markers of oxidative stress such as exhaled ethane and pentane (Nycyk et al, 1998;Pitkanen et al, 1990), serum HNE (Ogihara et al, 1999), F 2a -isoprostanes in tracheal aspirate or in plasma (Ahola et al, 2004), protein-carbonyl in bronchoalveolar fluid (Gladstone & Levine et al, 1994) or o-dityrosine in urine (Kelly & Lubec, 1995;Lubec et al, 1997). It has been suggested that some of these markers may be higher in the first few days of life in preterm infants who will develop BPD as compared to those who will not (Gladstone & Levine et al, 1994;Hodgman et al, 1969).…”