ENDOTOXIN-INDUCED INFLAMMATION DOES NOT CAUSE HEPATIC ZINC ACCUMULATION IN MICE LACKING METALLOTHIONEIN GENE-EXPRESSION

The action of endotoxin lipopolysaccharide (LPS) on hepatic Zn uptake was examined in mice lacking expression of metallothionein (MT)-I 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.