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The Influence of Zinc Status on the Levels of Metallothionein in Isolated Perfused Rat Liver¹

Section on Biochemistry, Division of Biochemistry, Physiology and Pharmacology, The University of South Dakota School of Medicine, Vermillion, South Dakota 57069

The levels of cadmium and zinc metallothionein in isolated perfused livers of zinc depleted and repleted rats were investigated. Rats (160–200 g or 90–120 g) were fed either a zinc-deficient or zinc-supplemented diet for 62 or 42 days. The 90 to 120 g rats were repleted with 30 ppm Zn²⁺ in the drinking water for 1, 4 and 10 days after 35 days of depletion, and another group after depletion for 21 days was repleted for 15 days on a 21% casein diet. At appropriate times livers were cannulated, removed and perfused ± 25 µg Cd²⁺ as CdCl₂, for 2 hours through the portal vein in a perfusion apparatus. Zinc depletion resulted in significant decreases in growth rate (1.4 versus 5.7 g/day) and liver weights. Repletion with Zn for 10 days increased the weight gain to 7.1 g/day. Depletion decreased the incorporation of Zn and Cd into metallothionein by 57 to 60%, while repletion for 1, 4 and 10 days increased the incorporation to nearly 500% of control levels. But, as repletion progressed, zinc in metallothionein fell to normal levels after 15 days. Cadmium in metallothionein did not decrease between 1 and 10 days of repletion. Zinc deficiency also reduced the zinc content of the liver by 44%, which increased to normal levels after 10 days of repletion. These data support the conclusion that zinc status can influence the incorporation of cadmium and zinc into metallothionein.

KEY WORDS: • zinc deficiency • zinc repletion • metallothionein • cadmium induction

¹ Supported by NIH Grant ES 01288 with funds provided by EPA [IAG-DS-E772] and Research Career Development Award ES 00022.

Manuscript received 29 January 1979.