Antioxidant enzymes are induced during recovery from acute lung injury.
OBJECTIVE
To determine the contribution of the pulmonary antioxidant defense enzymes of the hexose monophosphate (HMP) shunt and glutathione systems to recovery from oxidant-mediated lung injury in an animal model shown to closely resemble the clinical syndrome of acute respiratory distress syndrome.


METHODS
Prospective, controlled laboratory study on phorbol myristate acetate (PMA)-induced lung injury in rabbits.


METHODS
Animal research laboratory.


METHODS
Rabbits were injected with PMA (80 microg/kg) for 3 consecutive days. Control animals received normal saline.


RESULTS
Lungs were harvested at 24, 48, 72, and 96 hrs (n = 5/time point) after PMA injection or after the third injection of normal saline in control animals (n = 6). The cytosolic fraction from lung and bronchial alveolar lavage (BAL) fluid was used for measurements of HMP shunt and glutathione enzymes. Pulmonary activity peaked at 48 hrs post-PMA injury with a 40% increase in glucose-6-phosphate dehydrogenase activity and a 32% increase in 6-phosphogluconate dehydrogenase activity over control levels. BAL activity was maximal at 72 hrs with an increase of 98% in glucose-6-phosphate dehydrogenase and 346% in 6-phosphogluconate dehydrogenase activities. Glutathione peroxidase was maximally induced by 77% at 48 hrs in BAL and by 107% at 24 hrs in lung. Glutathione reductase activity did not increase significantly in either lung or BAL.


CONCLUSIONS
The observed induction of the antioxidant enzymes in response to PMA suggests that both the HMP shunt and the glutathione systems contribute to the recovery phase of oxidant-mediated lung injury. The inability of natural host defenses to regenerate reduced glutathione may explain failure of recovery from acute respiratory distress syndrome and suggests an avenue for clinical intervention.
Department of Surgery, UT-Houston School of Medicine, TX 77030, USA.
R A
RA
Kozar
C J
CJ
Weibel
J
J
Cipolla
A J
AJ
Klein
M M
MM
Haber
M Z
MZ
Abedin
S Z
SZ
Trooskin
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004790:Enzyme Induction; D005948:Glucose Dehydrogenases / Q000096:biosynthesis*; D005979:Glutathione Peroxidase / Q000096:biosynthesis*; D008297:Male; D010427:Pentose Phosphate Pathway; D011817:Rabbits; D012128:Respiratory Distress Syndrome / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity
D005948:Glucose Dehydrogenases; D005979:Glutathione Peroxidase; D013755:Tetradecanoylphorbol Acetate