title: Endotoxin-induced inflammation does not cause hepatic zinc accumulation in mice lacking metallothionein gene expression.
abstract: The action of endotoxin lipopolysaccharide (LPS) on hepatic Zn uptake was examined in mice lacking expression of metallothionein (MT)-1 and MT-II genes. Hepatic Zn concentrations, which in normal control mice increased by a mean 29% (MT elevated 20-fold) 16 h post-LPS exposure, did not increase in MT-null mice. Plasma Zn fell by 68% in controls and 32% in MT-null mice. The time course of LPS action in normal mice was characterized by a rapid reduction (-74% at 4 h, -81% at 8 h) and partial recovery (-39% at 24 h) in plasma Zn, with a progressive increase over 24 h in hepatic concentrations of MT (by 36-fold) and Zn (by 40%). In contrast, the MT-null mice had a linear decrease in plasma Zn (-15% at 8 h, -41% at 24 h) and early loss of Zn from the liver. The Zn changes seen in MT-null mice were largely attributable to LPS-associated anorexia. Food deprivation (20 h) alone caused respective 14% and 30% decreases in hepatic and plasma Zn concentrations and a 27% reduction in total liver Zn reserves, whereas fasted normal mice conserved Zn with a 4-fold increase in hepatic MT. This study confirms that MT synthesis is essential for endotoxin-induced liver Zn accumulation.
authors.affiliation: Division of Clinical Biochemistry, Institute of Medical and Veterinary Science, Adelaide, Australia.
authors.forename: J C
authors.initials: JC
authors.lastname: Philcox
authors.forename: P
authors.initials: P
authors.lastname: Coyle
authors.forename: A
authors.initials: A
authors.lastname: Michalska
authors.forename: K H
authors.initials: KH
authors.lastname: Choo
authors.forename: A M
authors.initials: AM
authors.lastname: Rofe
mesh_terms: D000818:Animals; D004926:Escherichia coli; D005508:Food Deprivation; D007249:Inflammation / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008668:Metallothionein / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015032:Zinc / Q000378:metabolism*
chemical_list: D008070:Lipopolysaccharides; D008668:Metallothionein; D015032:Zinc