Lipid peroxidation and antielastase activity in the lung under oxidant stress: role of antioxidant defenses.
The role of lipid peroxidation in the inactivation of alpha 1-protease inhibitor (alpha 1-PI) in the alveolar lining fluid of human subjects has been examined under oxidant stress. Exposure to nitrogen dioxide (NO2) at 4 ppm for 3 h resulted in a significant increase in the amount of lipid peroxidation products in the alveolar lining fluid, with conjugated dienes the predominant species. Four-week supplementation with vitamins C and E before NO2 exposure markedly decreased the levels of conjugated dienes (control 804 +/- 103 pmol/micrograms total phospholipids vs. vitamin-supplemented 369 +/- 58, P = 0.003). Malondialdehydes, although detectable in the lavage fluid, contributed little to the total amount of lipid peroxidation products, and the levels were comparable in both groups. NO2 exposure in the absence of vitamin supplementation caused a significant decrease in the elastase inhibitory capacity (EIC) of the alveolar lining fluid in the control group but not in the vitamin-supplemented group [control 3.67 +/- 0.32 micrograms alpha 1-PI/micrograms porcine pancreatic elastase (PPE) vs. vitamin-supplemented 2.75 +/- 0.17, P less than 0.03]. The vitamin-supplemented group had a lower level of conjugated dienes and a higher EIC. Conversely, the control group had higher levels of conjugated dienes and a lower EIC in their lavage fluid. These studies demonstrate that lipid peroxidation occurs as an early event during oxidant exposure in the lungs of normal subjects. The appearance of lipid peroxidation products in the lavage fluid is associated with a decrease in the EIC of the alveolar lining fluid. Vitamins C and E diminish lipid peroxidation and preserve the EIC of the lower respiratory tract fluid during oxidant stress.
Mohsenin
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John B. Pierce Laboratory, Yale University School of Medicine, New Haven, Connecticut 06519.
D000328:Adult; D000975:Antioxidants / Q000378:metabolism; D001205:Ascorbic Acid / Q000097:blood / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid / Q000378:metabolism; D005260:Female; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009585:Nitrogen Dioxide / Q000009:adverse effects; D010084:Oxidation-Reduction; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors*; D014810:Vitamin E / Q000097:blood / Q000494:pharmacology; D000515:alpha 1-Antitrypsin / Q000378:metabolism
D000975:Antioxidants; D000515:alpha 1-Antitrypsin; D014810:Vitamin E; D010196:Pancreatic Elastase; D001205:Ascorbic Acid; D009585:Nitrogen Dioxide