Mediation of endotoxin-induced changes in zinc metabolism in rats

A further characterization of endotoxin-induced changes in zinc metabolism provided insight into the possible mediation processes involved. Endotoxin reduced serum zinc levels while elevating zinc associated with hepatic metallothionein (Zn-MT) in control, fasted, and zinc-depleted rats. Unlike zinc, copper in the serum and that associated with metallothionein showed little response to endotoxin. In vitro translation of liver mRNA demonstrated that metallothionein mRNA levels were increased after endotoxin administration to either control or zinc-depleted rats. Cycloheximide fully blocked endotoxin-induced alterations in serum and metallothionein zinc, but actinomycin D was only partially inhibitory. Glucagon might act as the primary mediator for these actinomycin D-insensitive changes. Glucocorticoids might be responsible for the remaining alterations in zinc metabolism because dexamethasone increased 65Zn accumulation in cultured hepatocytes, whereas endotoxin did not. In endotoxin-treated rats, the kidney as well as liver showed increases in metallothionein-zinc and metallothionein-mRNA. Virtually all the effects of endotoxin were mimicked by leukocytic endogenous mediator, implying that it probably represents the initial mediator of endotoxin action on zinc metabolism.