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Prophylaxis against lipopolysaccharide-induced acute lung injury by alpha-tocopherol liposomes
1Operational Medicine Sector, Defence and Civil Institute of Environmental Medicine, Toronto, ON, Canada.
Objective:
To investigate whether intravenously administered liposomal alpha-tocopherol can protect the lung from the injurious action of Escherichia coli lipopolysaccharide (LPS).
Design:
Prospective, randomized animal study.
Setting:
Government research laboratory.
Subjects:
Twenty adult male Sprague-Dawley rats.
Interventions:
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.
Measurements And Main 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.
Conclusion:
These results suggest that augmentation of the pulmonary antioxidant status can ameliorate LPS-induced lung injuries mediated by oxidative stress mechanisms.