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.
DESIGN: Prospective, controlled laboratory study on phorbol myristate acetate (PMA)-induced lung injury in rabbits.
SETTING: Animal research laboratory.
SUBJECTS: Rabbits were injected with PMA (80 microg/kg) for 3 consecutive days. Control animals received normal saline.
MEASUREMENTS AND MAIN 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.