AJP - Endocrinology and Metabolism, Vol 247, Issue 4 436-E441, Copyright © 1984 by American Physiological Society
Mediation of endotoxin-induced changes in zinc metabolism in rats
R. A. DiSilvestro and R. J. Cousins
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.
