Dietary vitamin E does not protect from endotoxin-induced hepatic microvascular dysfunction

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) alpha-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.

Effect of multivitamins in an effervescent preparation on the respiratory burst of peritoneal macrophages in mice

“…Although these vitamins are effective antioxidants in vitro, the results of in vivo and ex vivo studies are conflicting (McCall & Frei, 1999). An a-tocopherol acetate-enriched or -deficient diet failed to significantly activate Kupffer cell phagocytosis and to influence liver injury in rats (Rücker et al 1997). Vitamin C when incubated in vitro neutralized the free radicals produced during respiratory burst of murine peritoneal phagocytic cells, but showed no effect on ROS production in cells harvested from mice pretreated with high doses of the vitamin in vivo (Arquette & Caren, 1992).…”