alpha-tocopherol improves impaired physiology of rat type II pneumocytes isolated from experimentally injured lungs.
BACKGROUND
Oxidant stress delivered by nitrogen dioxide (NO2) inhalation impairs the function of extracellular surfactant as well as surfactant phospholipid metabolism in type II pneumocytes. Because protection against oxidant stress is important to normal lung function, the lung contains a variety of antioxidants, including vitamin E. Whether administration of this antioxidant during NO2 inhalation attenuates NO2-induced alterations in phospholipid metabolism in type II pneumocytes has not been studied.


METHODS
We exposed rats to identical NO2 body doses (720 p.p.m. x h) using continuous, intermittent, or repetitive protocols. During exposure periods, the animals received daily intramuscular injections of vitamin E (25 mg kg-1). We isolated type II pneumocytes from NO2-exposed rats and evaluated them for cell yield and viability, as well as for synthesis and secretion of phosphatidylcholine (PC) as measures of surfactant metabolism.


RESULTS
The yield of type II pneumocytes was significantly elevated from animals that had been exposed continuously to NO2 whereas in intermittently and repeatedly exposed rats, cell yield was similar to yield from control animals. Viability of the isolated cells was similar in controls and all NO2 exposure protocols. Vitamin E treatment of the NO2-exposed rats neither changed cell yield nor cell viability. Phospholipid de novo synthesis, as estimated by choline incorporation into PC, was increased most after continuous NO2 inhalation whereas in the other conditions there was only a slight increase. Vitamin E administration further increased phospholipid synthesis; this difference reached statistical significance only in the case of intermittent NO2 exposure. Secretion of phosphatidylcholine from type II cells was only reduced after continuous NO2 inhalation and administration of the antioxidant reduced the impairment.


CONCLUSIONS
Because vitamin E appears to preserve the ability of type II pneumocytes isolated from NO2-exposed rats to synthesize and secrete surfactant lipid, we conclude that administration of vitamin E may mitigate NO2-induced lung injury.
Müller
B
B
Philipps University of Marburg, Marburg, Germany. bmueller@mailer.unimarburg.de
Hochscheid
R
R
Seifart
C
C
Barth
P J
PJ
D000280:Administration, Inhalation; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001991:Bronchitis / Q000139:chemically induced / Q000188:drug therapy; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002794:Choline / Q000378:metabolism; D004195:Disease Models, Animal; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D055370:Lung Injury; D008297:Male; D009585:Nitrogen Dioxide / Q000008:administration & dosage / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D010713:Phosphatidylcholines / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014810:Vitamin E / Q000494:pharmacology* / Q000627:therapeutic use
D000975:Antioxidants; D010713:Phosphatidylcholines; D014810:Vitamin E; D007770:L-Lactate Dehydrogenase; D002794:Choline; D009585:Nitrogen Dioxide