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Iron-Induced Metallothionein in Chick Liver: A Rapid, Route-Dependent Effect Independent of Zinc Status^{1 ,2}

Department of Poultry and Avian Sciences and Division of Nutrition, Cornell University, Ithaca, NY 14853 ^* Department of Biochemistry, University of Kansas Medical Center, Kansas City, KS 66103

The induction of hepatic metallothionein (MT) by the parenteral administration of iron was studied. Iron administered to chicks by intravenous or subcutaneous injection caused a 1.9-fold increase in hepatic MT. In marked contrast, intraperitoneal (ip) Fe resulted in a 10-fold increase, thus demonstrating the importance of the route of metal administration. This route-dependent effect was found to be dose-dependent, with ip injections between 1 and 10 mg Fe/kg resulting in a linear increase in MT and a concomitant reduction in serum zinc concentration and feed intake. High ip doses of Fe resulted in a persistent depression in serum Zn and elevated MT and MTmRNA. Equimolar ip injections of either Zn or Fe showed similar patterns of MTmRNA accumulation. In both cases MTmRNA levels were elevated by 3 h, with a peak at 6 h postinjection (Fe 8-fold, Zn 12-fold above 0 h). Plasma Zn was maximally reduced by Fe at 9 h (60%). The MT induction by Fe, as well as related depression in plasma Zn, was completely inhibited by actinomycin D. Zn depletion eliminated the accumulation of hepatic Zn and MT protein following ip injection of Fe or endotoxin, but not of cadmium, despite marked elevation of hepatic MTmRNA. Our results demonstrate Fe injected into the body cavity of chicks results in a rapid induction of hepatic MT that, like endotoxin induction, is independent of dietary Zn status.

KEY WORDS: • metallothionein • liver • iron • endotoxin • chicks

¹ Some of the data contained in this report were presented at the 1988 annual meeting of the American Institute of Nutrition held in Las Vegas, NV. [FLEET, J. C., ANDREWS, G. K. & McCORMICK, C. C. (1988) Similarities in the route-dependent induction of hepatic metallothionein by copper, zinc, and iron. FASEB J. 2: A634 (abs.)].

² This work was supported in part by a grant from the Biotechnology Institute, Cornell University.

³ Present address: Bioavailability Laboratory. The U.S. Department of Agriculture, Human Nutrition Research Center on Aging at Tufts University, 711 Washington St., Boston, MA 02111

⁴ To whom correspondence should be addressed.

Manuscript received 21 February 1989. Revision accepted 19 March 1990.

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