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-Tocopherol liposomes alleviate LPS-induced hepatotoxicities

Operational Medicine Sector, Defence and Civil Institute of Environmental Medicine, North York, Ontario, Canada

P.N. Shek

Operational Medicine Sector, Defence and Civil Institute of Environmental Medicine, North York, Ontario, Canada, Department of Clinical Biochemistry, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada

Gram-negative bacteria, in part through lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF), activate phagocytes to generate reactive oxygen species (ROS), which have been known to play a key role in the pathogenesis of liver injury. Accordingly, we hypothesized that the susceptibility of the liver to ROS should be reduced by augmenting its antioxidant status. Adult male Sprague-Dawley rats were pretreated with -tocopherol liposomes (20 mg -tocopherol/kg body weight, i.v.), plain liposomes or saline. 24 h after liposomal treatment, rats were injected intravenously with LPS (1 mg/kg, Escherichia coli: 0111:B4) and killed 2 h later. Livers of saline-pretreated animals challenged with LPS were damaged as demonstrated by increases in plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities. The hepatic injury appeared to be associated with oxidative stress-mediated mechanisms as evidenced by increases in lipid peroxidation and decreases in glutathione concentration in the liver, both indices of oxidative stress. Also, LPS injection resulted in increases in plasma TNF and thromboxane B₂ (TXB₂) levels, as well as increases in hepatic myeloperoxidase (MPO) activity and chloramine concentration, suggestive of activation of the inflammatory response. Pretreatment of rats with plain liposomes, 24 h prior to LPS challenge, failed to protect against the LPS-induced liver injury. Although pretreatment of animals with -tocopherol liposomes was not effective in preventing the LPS-induced inflammatory response, it conferred a partial protection against the LPS-induced changes in plasma AST and ALT activities as well as in hepatic levels of lipid peroxidation, glutathione and chloramine concentrations. These data appear to suggest that augmentation of the hepatic antioxidant status is effective in alleviating the LPS-induced liver injury.

Journal of Endotoxin Research, Vol. 3, No. 6, 505-512 (1996)
DOI: 10.1177/096805199600300609


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