Dietary vitamin E does not protect from endotoxin-induced hepatic microvascular dysfunction |
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Authors: | M Rücker B Finckh A Kohlschütter M D Menger B Vollmar |
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Institution: | (1) Institute for Clinical and Experimental Surgery, University of Saarland, D-66421 Homburg/Saar (Germany), Fax +49 6841 166553, e-mail: exbvol@med-rz.uni-sb.de, DE;(2) Clinic for Paediatrics, University of Hamburg, D-20246 Hamburg (Germany), DE |
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Abstract: | Starting from the concept that lipopolysaccharide (LPS)-associated hepatotoxicity involves the action of reactive oxygen
species, the present study was conducted to test whether vitamin E, a lipophilic antioxidant, prevents LPS-induced hepatic
microvascular dysfunction and liver injury. Fifty-two rats were divided into three groups and fed diets containing 0 (n=16),
75 (n=18) or 8000 mg (n=18) α-tocopherol acetate/kg food for four weeks. At 1 h and 6 h after intravenous LPS-exposure (10
mg/kg E. coli LPS) hepatic microvascular response and liver injury were assessed by the analysis of Kupffer cell phagocytic activity, leukocyte-endothelial
cell interaction and nutritive sinusoidal perfusion (intravital fluorescence epi- illumination technique) as well as bile
flow, serum liver enzyme activities and tissue histomorphology. In animals fed with 75 mg vitamin E/kg (standard diet), LPS
caused hepatic Kupffer cell activation (increased phagocytic activity) and hepatic microvascular leukocyte activation, with
stasis in sinusoids and adherence in postsinusoidal venules (1 h) followed by leukocytic infiltration into tissue (6 h) and
progredient sinusoidal perfusion failure (6 h). Hepatic microvascular injury was accompanied by reduced bile flow and enhanced
liver enzyme release. Vitamin E-enriched diet (8000 mg/kg) and even vitamin E-deficient diet did not significantly affect
LPS-induced hepatic microvascular cell activation and perfusion failure. Thus, we conclude, that vitamin E is not effective
to protect from endotoxin-induced hepatic microvascular dysfunction.
Received 7 November 1996; received after revision 30 December 1996; accepted 20 January 1997 |
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Keywords: | , Vitamin E, α,-tocopherol acetate, scavenger, reactive oxygen species, leukocyte-endothelial cell interaction, Kupffer,,,,,cell, microcirculation, liver, |
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