Prophylaxis against lipopolysaccharide-induced acute lung injury by alpha-tocopherol liposomes.
OBJECTIVE
To investigate whether intravenously administered liposomal alpha-tocopherol can protect the lung from the injurious action of Escherichia coli lipopolysaccharide (LPS).


METHODS
Prospective, randomized animal study.


METHODS
Government research laboratory.


METHODS
Twenty adult male Sprague-Dawley rats.


METHODS
Animals were intravenously pretreated with alpha-tocopherol liposomes (20 mg alpha-tocopherol/kg body weight), plain liposomes, or saline. Twenty-four hours later, pretreated animals were challenged with an intravenous injection of LPS (E. coli 0111:B4, 1 mg/kg body weight), and killed 2 hrs after LPS challenge.


RESULTS
Challenge of saline-pretreated animals with LPS resulted in lung injuries as evidenced by an increase in wet lung weight and a reduction in pulmonary angiotensin converting enzyme (25%) and alkaline phosphatase (28%), injury markers of lung endothelial and epithelial type II cells, respectively. Also, LPS administration resulted in an increase in pulmonary myeloperoxidase and protease activities, indicative of a neutrophilic inflammatory response. Pretreatment of animals with liposomal alpha-tocopherol significantly attenuated the LPS-induced edematous lung weight response, and reduced the extent of injuries to the pulmonary endothelial and epithelial cells, demonstrated by a significantly smaller reduction in the corresponding enzyme marker activities.


CONCLUSIONS
These results suggest that augmentation of the pulmonary antioxidant status can ameliorate LPS-induced lung injuries mediated by oxidative stress mechanisms.
Suntres
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Operational Medicine Sector, Defence and Civil Institute of Environmental Medicine, Toronto, ON, Canada.
Shek
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PN
D000208:Acute Disease; D000818:Animals; D004337:Drug Carriers; D004926:Escherichia coli; D007275:Injections, Intravenous; D008070:Lipopolysaccharides / Q000009:adverse effects / Q000037:antagonists & inhibitors*; D008081:Liposomes; D008168:Lung / Q000187:drug effects* / Q000201:enzymology; D008171:Lung Diseases / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D011654:Pulmonary Edema / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014810:Vitamin E / Q000008:administration & dosage*
D004337:Drug Carriers; D008070:Lipopolysaccharides; D008081:Liposomes; D014810:Vitamin E; D009195:Peroxidase