PMID- 8021813
OWN - NLM
STAT- MEDLINE
DCOM- 19940801
LR  - 20190710
IS  - 0022-3573 (Print)
IS  - 0022-3573 (Linking)
VI  - 46
IP  - 2
DP  - 1994 Feb
TI  - Depletion of pulmonary glutathione using diethylmaleic acid accelerates the 
      development of oxygen-induced lung injury in term and preterm guinea-pig 
      neonates.
PG  - 98-102
AB  - Dietary or chemical depletion of pulmonary glutathione in adult rats and mice, 
      has been demonstrated to exacerbate the toxic effects of high oxygen 
      concentrations. The present paper has examined this phenomenon in a guinea-pig 
      model of prematurity, using the electrophilic agent diethylmaleic acid (DEM) to 
      provide a transient (up to 12 h) pulmonary glutathione depletion. Full-term and 
      3-days preterm guinea-pig pups were studied to assess the possible role for 
      glutathione deficiency as a mechanism mediating the increased susceptibility of 
      the immature lung to oxygen free-radical damage. The administration of DEM to 
      guinea-pig neonates depleted lung glutathione by 90% (term) or 68% (preterm) over 
      2 h. On exposure of pups to 95% oxygen for 48 h, DEM increased the incidence of 
      oxygen-related death to 31% in term pups and 100% in preterm pups. Term pups 
      exposed to hyperoxia and treated with DEM showed evidence of pulmonary injury, 
      indicated by an influx of neutrophils into the lung airspaces, and elevated 
      microvascular permeability. Control pups exposed to 95% oxygen were found to have 
      uninjured lungs after 48 h. We conclude that glutathione is an essential 
      component of the pulmonary antioxidant array in neonates. Glutathione may be of 
      particular importance in the early phase of oxygen exposure. The deficiency of 
      lung glutathione observed in preterm animals may account for their increased 
      susceptibility to oxygen-induced pulmonary injury.
FAU - Langley, S C
AU  - Langley SC
AD  - Department of Human Nutrition, University of Southampton, UK.
FAU - Kelly, F J
AU  - Kelly FJ
LA  - eng
GR  - Wellcome Trust/United Kingdom
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Pharm Pharmacol
JT  - The Journal of pharmacy and pharmacology
JID - 0376363
RN  - 0 (Maleates)
RN  - G81WQB56OL (diethyl maleate)
RN  - GAN16C9B8O (Glutathione)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Bronchoalveolar Lavage Fluid/cytology
MH  - Female
MH  - Fetus/drug effects/metabolism
MH  - Glutathione/*metabolism
MH  - Guinea Pigs
MH  - Leukocyte Count/drug effects
MH  - Lung/*drug effects/embryology/*metabolism
MH  - Male
MH  - Maleates/*pharmacology
MH  - Oxygen/*toxicity
MH  - Pregnancy
MH  - Pregnancy, Animal/*drug effects
MH  - *Prenatal Exposure Delayed Effects
EDAT- 1994/02/01 00:00
MHDA- 1994/02/01 00:01
CRDT- 1994/02/01 00:00
PHST- 1994/02/01 00:00 [pubmed]
PHST- 1994/02/01 00:01 [medline]
PHST- 1994/02/01 00:00 [entrez]
AID - 10.1111/j.2042-7158.1994.tb03749.x [doi]
PST - ppublish
SO  - J Pharm Pharmacol. 1994 Feb;46(2):98-102. doi: 
      10.1111/j.2042-7158.1994.tb03749.x.