Effect of Methyl Prednisolone on Normobaric Pulmonary Oxygen Toxicity in Rats

Halpern, Pinchas; Teitelman, U; Lanir, Amos

doi:10.1159/000194816

Cited by 7 publications

(4 citation statements)

References 12 publications

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“…Our findings of improved survival after dexamethasone are different from several studies in the adult rat, in which both Yam and Roberts [9] and Halpern et al [10] found increased oxygen toxicity and a significant decrease in survival in steroid-treated O 2 -exposed rats when compared to O 2 controls. Other studies involving different animal species and different study protocols were similar in reporting either no improvement or even increased toxicity and decreased survival during hyperoxia with dexamethasone treatment [11,12].…”

Section: Discussioncontrasting

confidence: 99%

“…Timing of administration may also affect pulmonary outcome. Studies in the adult rat of dexamethasone treatment for hyperoxic lung injury have shown either no improvement or worsening of survival when dexamethasone was begun at the onset of hyperoxic exposure [9][10][11][12]. However, Koizumi et al [13] showed improved survival if dexamethasone was begun later after pulmonary inflammation had occurred.…”

Section: Introductionmentioning

confidence: 99%

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Effects of Postnatal Dexamethasone on Oxygen Toxicity in Neonatal Rats

Dallas

Keeney²,

Mathews³

et al. 2004

Neonatology

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We investigated the effect of timing of early postnatal dexamethasone on survival of hyperoxia-exposed neonatal rats. Pups <24 h old were treated with a tapering course of dexamethasone or saline beginning either prior to exposure (day 0), or after 2, 4, or 6 days of ≧98% O₂ (n = 11–14) or air (n = 8–11). Exposures were continued for 14 days. By day 14, day 0 pups had poor survival regardless of the exposure (14% in O₂, 13% in air). Survival of pups treated with dexamethasone after 2, 4 and 6 days of O₂ exposure was significantly higher at 14 days (50, 86 and 79%, respectively) compared to saline O₂ controls (9%, p < 0.001 for each). Pulmonary biochemical analyses were conducted after exposure for 7 days in rat pups treated with dexamethasone or saline beginning after 4 days of exposure to air or O₂(n = 11–12 for each group). While pups treated with dexamethasone showed greatly improved survival compared to O₂ controls, there was no decrease in neutrophil influx into the lung as measured by lung myeloperoxidase and neutrophil counts in histologic specimens and lavage fluid. Catalase, glutathione peroxidase, total and manganese superoxide dismutase activities as well as manganese superoxide dismutase (MnSOD) mRNA expression were elevated in both O₂ groups after 7 days compared to the air groups (p < 0.05) and MnSOD mRNA expression was elevated in the O₂/dexamethasone group, but there were no differences between dexamethasone and saline groups in O₂. Thus, this study indicates that the timing of dexamethasone administration is crucial. Mechanisms other than increases in antioxidant enzymes or decreases in lung neutrophils underlie the ability of dexamethasone to improve survival of these neonatal rats.

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Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effects of Postnatal Dexamethasone on Oxygen Toxicity in Neonatal Rats

Dallas

Keeney²,

Mathews³

et al. 2004

Neonatology

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“…Koizumi et al (16) have shown that dexamethasone improved survival and decreased lung damage if given when exposure to hyperoxia was to be soon terminated; however, dexamethasone worsened lung damage and diminished survival if given early during exposure to hyperoxia. On the other hand, Halpern et al (11) reported that rats receiving MP (10-60 mg · kg Ϫ1 · day Ϫ1 ) survived for less time than control rats.…”

Section: Discussionmentioning

confidence: 99%

Effect of steroid on hyperoxia-induced ICAM-1 expression in pulmonary endothelial cells

Suzuki¹,

Nishio²,

Takeshita

et al. 2000

American Journal of Physiology-Lung Cellular and Molecular Phys

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Intercellular adhesion molecule-1 (ICAM-1) of the vascular endothelium plays a key role in the development of pulmonary oxygen toxicity. We studied the effect of steroid on hyperoxia-induced ICAM-1 expression using cultured endothelial cells in vitro. Human pulmonary artery endothelial cells (HPAECs) were cultured to confluence, and then the monolayers were exposed to either control (21% O(2)-5% CO(2)) or hyperoxic (90% O(2)-5% CO(2)) conditions with and without a synthetic glucocorticoid, methylprednisolone (MP). MP reduced hyperoxia-induced ICAM-1 and ICAM-1 mRNA expression in a dose-dependent manner. Neutrophil adhesion to hyperoxia-exposed endothelial cells was also inhibited by MP treatment. In addition, MP attenuated hyperoxia-induced H(2)O(2) production in HPAECs as assessed by flow cytometry. An electrophoretic mobility shift assay demonstrated that hyperoxia activated nuclear factor-kappaB (NF-kappaB) but not activator protein-1 (AP-1) and that MP attenuated hyperoxia-induced NF-kappaB activation dose dependently. With Western immunoblot analysis, IkappaB-alpha expression was decreased by hyperoxia and increased by MP treatment. These results suggest that MP downregulates hyperoxia-induced ICAM-1 expression by inhibiting NF-kappaB activation via increased IkappaB-alpha expression.

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“…In view of the large number of reports appearing in the recent pediatric literature about the clinical use of DEX postnatally to try to reduce the incidence and severity of BPD (41)(42)(43)(44), it is very important to point out here that DEX treatment appears to act very differently on the course ofexperimental pulmonary O 2 toxicity when it is administered prenatally (present studies) than when it is administered postnatally during the period of high O 2 exposure. When used as a treatment agent during hyperoxia, there is very convincing evidence from animal studies in a variety of species that DEX treatment, rather than having a protective effect, in fact tends to markedly accelerate the development of Os-induced lung damage and lethality (31,(45)(46)(47).…”

Section: Discussionmentioning

confidence: 99%

Prenatal Dexamethasone Treatment Improves Survival of Newborn Rats during Prolonged High O2 Exposure

Frank

1992

Pediatr Res

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ABSTRACT. Prenatal dexamethasone (DEX) treatment is known to accelerate the maturation of both the surfactant system and the fetal lung antioxidant enzyme (AOE) system (Frank L, Lewis P, Sosenko IRS: Pediatrics 75: [569][570][571][572][573][574] 1985). Because of this stimulatory effect of prenatal DEX on the normal late gestational development of the AOE system, we questioned whether this treatment might have a salutary effect on the ability of the newborn rat to tolerate early and prolonged exposure to hyperoxia, inasmuch as the AOE are the primary lung defensive system against high O 2 challenge. In nine experiments with term newborn rats in >95% O 2 , the composite percentage of survival was significantly greater in the prenatal DEX pups at all time periods in hyperoxia from 7 d [control pups, 67 of 94 (71%); prenatal DEX, 96 of 99 (97%») to 14 d [controls, 10 of 32 (31%); prenatal DEX, 18 of 33 (55%») (p < 0.01). In addition to survival per se, the prenatal DEX pups showed significantly decreased lung wet weight/dry weight ratios, pathologic evidence of pulmonary edema, and lung conjugated dienes versus the O2 control newborn group. Of the many comparative parameters examined, the major difference found between the two groups was in the pulmonary AOE responses to hyperoxia. By 2 d in hyperoxia, the prenatal DEX rat pups showed significantly elevated superoxide dismutase, catalase, and glutathione peroxidase activities compared to air control pups, and at 4 and 7 d in O 2 the AOE levels were consistently greater in the DEX group than the AOE responses in the control O2 pups. The more rapid and more pronounced AOE response to hyperoxic challenge may help to explain the substantial protective effect of prenatal DEX versus newborn O 2 toxicity. immature infant. Administration of a long-acting glucocorticoid for 48 h before premature delivery may successfully stimulate surfactant production/secretion in the immature fetal lung and lessen the chance of serious respiratory distress syndrome in the prematurely delivered newborn (1).Previous work from our laboratories has demonstrated that the prenatal administration of DEX to pregnant rats will not only accelerate the late gestational development of the surfactant system in the rat fetuses, but will also accelerate the normal late gestational development of the fetal lung AOE system (2). The late gestational rise in fetal lung SOD, CAT, and GP activities, now demonstrated to be a natural maturational occurrence in five animal species (rat, mouse, rabbit, hamster, and sheep) (3-8), is proposed to be the biochemical means by which the lung is prepared for its safe transition from the quite hypoxic in utero environment to the relatively Os-rich ex utero environment it will encounter immediately at birth (3-5, 9).Because of its marked stimulatory effect on fetal lung AOE system development, we wondered if prenatal DEX treatment might also have a salutary effect on the ability of the newborn animal to tolerate early and prolonged exposure to hyperoxia. We describe herei...

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Effect of Methyl Prednisolone on Normobaric Pulmonary Oxygen Toxicity in Rats

Cited by 7 publications

References 12 publications

Effects of Postnatal Dexamethasone on Oxygen Toxicity in Neonatal Rats

Effects of Postnatal Dexamethasone on Oxygen Toxicity in Neonatal Rats

Effect of steroid on hyperoxia-induced ICAM-1 expression in pulmonary endothelial cells

Prenatal Dexamethasone Treatment Improves Survival of Newborn Rats during Prolonged High O2 Exposure

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