Alpha-tocopherol and superoxide dismutase suppress and diethyldithiocarbamate and phorone enhance the lipopolysaccharide-induced increase in N1-acetylspermidine concentrations in mouse liver.
Previously, we have shown the close association between hepatic concentrations of N1-acetylspermidine and the radical-producing potency of several drugs. Since vitamin E, superoxide dismutase (SOD), and reduced glutathione (GSH) are known to scavenge free radicals, in this study we tested the effect of alpha-tocopherol, one of the most potent vitamin E isomers, and SOD on the lipopolysaccharide (LPS)-induced increase in hepatic concentrations of N1-acetylspermidine. The LPS-induced increase in hepatic N1-acetylspermidine was more than twice as great in vitamin E-deficient mice as in vitamin E-supplemented mice. Pretreatment with alpha-tocopherol suppressed the LPS-induced increase in hepatic N1-acetylspermidine in vitamin E-deficient mice. Alpha-tocopherol and SOD given to mice maintained on a usual diet likewise suppressed the LPS-induced increase in hepatic N1-acetylspermidine and putrescine. The hepatic concentrations of alpha-tocopherol and GSH were lower in LPS-treated mice than in control animals. Diethyldithiocarbamate, an inhibitor of SOD, and diisopropylidene (phorone), a GSH-depleting agent, enhanced the LPS-induced increase in hepatic N1-acetylspermidine. These results suggest that the LPS-induced hepatic increase in N1-acetylspermidine is connected with radical-induced injury in vivo and that superoxide anion is produced in the liver of LPS-treated mice.
Sugimoto
H
H
Department of Physiology, Institute of Endocrinology, Gunma University, Maebashi, Japan.
Matsuzaki
S
S
Hamana
K
K
Yamada
S
S
Kobayashi
S
S
D000818:Animals; D004050:Ditiocarb / Q000494:pharmacology*; D016166:Free Radical Scavengers; D007659:Ketones / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D012475:Salmonella; D013095:Spermidine / Q000031:analogs & derivatives* / Q000378:metabolism; D013482:Superoxide Dismutase / Q000494:pharmacology*; D014810:Vitamin E / Q000494:pharmacology*; D014811:Vitamin E Deficiency / Q000378:metabolism
D016166:Free Radical Scavengers; D007659:Ketones; D008070:Lipopolysaccharides; D014810:Vitamin E; C017988:N(1)-acetylspermidine; C018637:phorone; D004050:Ditiocarb; D013482:Superoxide Dismutase; D013095:Spermidine