Prophylaxis against lipopolysaccharide-induced acute lung injury by alpha-tocopherol liposomes

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Abstract

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. (Crit Care Med 1998; 26:723-729)

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