Alpha-tocopherol attenuates lipopolysaccharide-induced sickness behavior in mice.
Antioxidants protect cells from oxidative damage and reduce lipopolysaccharide (LPS)-induced expression of inflammatory cytokines. Because inflammatory cytokines induce sickness behavior, we hypothesized that antioxidants, namely alpha-tocopherol (alpha-T) and selenium would inhibit sickness behavior caused by LPS. In an initial study, mice were injected intraperitoneal (i.p.) with vehicle, 2, or 20mg alpha-T for 3 consecutive days and then challenged with vehicle, 1, 10, or 100 microg of LPS. Sickness behavior was quantified by measuring social exploratory behavior. Vehicle pretreated mice injected with LPS showed a marked reduction in social behavior at 4h (p < .01). However, sickness behavior induced by the lowest dose of LPS was partially or completely blocked by 2 or 20mg alpha-T, respectively. alpha-T did not prevent sickness from higher doses of LPS. In a second study, mice were fed AIN93-M modified diets containing 10, 75, and 500 mg alpha-T/kg and 0.05, 0.15, and 2mg selenium/kg for 8 weeks and then challenged with saline or LPS (1 microg). The highest concentration of dietary alpha-T and selenium tended (p = .1) to reduce LPS-induced sickness behavior. Mice fed diets low in antioxidants had reduced plasma alpha-T levels and glutathione peroxidase activity (p = .08 and p < .01, respectively) and elevated liver thiobarbituric acid reactive substances (p < .001) 24h post LPS. Collectively, these data indicate that alpha-T improved the oxidative status after exposure to LPS, which may explain its ability to ameliorate symptoms of sickness.
Berg
Brian M
BM
Division of Nutritional Sciences, University of Illinois, Urbana, IL 61801, USA.
Godbout
Jonathan P
JP
Kelley
Keith W
KW
Johnson
Rodney W
RW
D000704:Analysis of Variance; D000821:Animal Feed; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005106:Exploratory Behavior / Q000187:drug effects*; D005979:Glutathione Peroxidase / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012643:Selenium / Q000494:pharmacology; D012919:Social Behavior; D024502:alpha-Tocopherol / Q000008:administration & dosage*
D000975:Antioxidants; D008070:Lipopolysaccharides; D005979:Glutathione Peroxidase; D024502:alpha-Tocopherol; D012643:Selenium