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 Es cherichia coli lipopolysaccharide (LPS). Design: Prospective, randomiz ed animal study. Setting: Government research laboratory. Subjects: Tw enty adult male Sprague Dawley rats. Interventions: Animals were intra venously pretreated with alpha-tocopherol liposomes (20 mg alpha-tocop herol/kg body weight), plain liposomes, or saline. Twenty-four hours l ater, pretreated animals were challenged with an intravenous injection of LPS (E. coil 0111:B4, 1 mg/kg body weight), and killed 2 hrs after LPS challenge. Measurements and Main Results: Challenge of saline pre treated animals with LPS resulted in lung injuries as evidenced by an increase in wet lung weight and a reduction in pulmonary angiotensin c onverting 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 myeloperoxidas e and protease activities, indicative of a neutrophilic inflammatory r esponse, Pretreatment of animals with liposomal alpha-tocopherol signi ficantly attenuated the LPS induced edematous lung weight response, an d reduced the extent of injuries to the pulmonary endothelial and epit helial cells, demonstrated by a significantly smaller reduction in the corresponding enzyme marker activities. Conclusion: These results sug gest that augmentation of the pulmonary antioxidant status can amelior ate LPS-induced lung injuries mediated by oxidative stress mechanisms.