Dexamethasone treatment fails to reduce oxygen-induced lung injury in the preterm guinea pig

Town, G. Ian; Phillips, Gary; Landreau, M.; Louden, Jonathan D.; Holgate, Stephen T.; Kelly, Frank J.

doi:10.1016/0006-2952(93)90324-p

Cited by 9 publications

(3 citation statements)

References 34 publications

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“…To our knowledge, only one other study has examined antioxidant enzyme activities in animals treated postnatally with dexamethasone. Town et al [37] evaluated the effects of dexamethasone treatment of preterm guinea pigs exposed to hyperoxia. Daily dexamethasone was given to pups exposed to hyperoxia or air for 3 days followed by 4 days of recovery in air.…”

Section: Discussionmentioning

confidence: 99%

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: Discussionmentioning

confidence: 99%

Effects of Postnatal Dexamethasone on Oxygen Toxicity in Neonatal Rats

Dallas

Keeney²,

Mathews³

et al. 2004

Neonatology

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“…34,36,37 One study used a double hit model combining prenatal LPS and hyperoxia, whereas another study in guinea pigs combined prematurity with hyperoxia. 37,74 All other studies made use of healthy newborn animals. Twelve studies (24%) used retinoic acid as a co-intervention.…”

Section: Study Selectionmentioning

confidence: 99%

Effects of postnatal corticosteroids on lung development in newborn animals. A systematic review

Lok,

Wever,

Vliegenthart

et al. 2024

Pediatr Res

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Background Postnatal systemic corticosteroids reduce the risk of bronchopulmonary dysplasia but the effect depends on timing, dosing, and type of corticosteroids. Animal studies may provide valuable information on these variable effects. This systematic review summarizes the effects of postnatal systemic corticosteroids on lung development in newborn animals. Methods A systematic search was performed in PubMed and Embase in December 2022. The protocol was published on PROSPERO (CRD42021177701). Results Of the 202 eligible studies, 51 were included. Only newborn rodent studies met the inclusion criteria. Most studies used dexamethasone (98%). There was huge heterogeneity in study outcome measures and corticosteroid treatment regimens. Reporting of study quality indicators was mediocre and risk of bias was unclear due to poor reporting of study methodology. Meta-analysis showed that postnatal corticosteroids caused a decrease in body weight as well as persistent alveolar simplification. Subgroup analyses revealed that healthy animals were most affected. Conclusion In newborn rodents, postnatal systemic corticosteroids have a persistent negative effect on body weight and lung development. There was huge heterogeneity in experimental models, mediocre study quality, unclear risk of bias, and very small subgroups for meta-analysis which limited firm conclusions. Impact Postnatal corticosteroids reduce the risk of bronchopulmonary dysplasia but the effect depends on timing, dosing, and type of corticosteroids while the underlying mechanism of this variable effect is unknown. This is the first systematic review and meta-analysis of preclinical newborn animal studies reviewing the effect of postnatal systemic corticosteroids on lung development. In newborn rodent models, postnatal corticosteroids have a persistent negative effect on body weight and lung alveolarization, especially in healthy animals.

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“…As such, these and other preclinical studies may have contributed to the enthusiasm for the evaluation of dexamethasone in the management of preterm birth. However, postnatal administration of dexamethasone failed to reduce oxygen-induced lung injury in preterm guinea pigs [39], indicating the existence of preclinical studies that also spoke against the use of dexamethasone in preterm infants.…”

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confidence: 99%