Metallothionein animal

Currently available CRMs There exist a limited number of commercial calibrants of animal metallothioneins. 

Small-molecule antioxidants include glutathione, ascorbic acid (vitamin C), vitamin E and a number of dietary flavonoids. Because humans, in contrast to most other animals, are unable to synthesize vitamin C, this important antioxidant must be supplied entirely from dietary intake. Other proteins, such as thioredoxin and metallothionein, may also contribute to some extent to the cellular antioxidant pool. 

Birds are comparatively resistant to the biocidal properties of cadmium. Adult drake mallards (Anas platyrhynchos) fed up to 200 mg cadmium per kg diet for 90 days all survived with no loss of body weight (White and Linley 1978). Laying hens fed 200 mg Cd/kg diet also survived egg production was suppressed at that concentration but not at lower concentrations (White and Linley 1978). Marine and terrestrial animals, including ducks, have been shown to be particularly abundant in a wildlife community associated with a marine sewer outfall (Brown et al. 1977). These animals were contaminated with high levels of cadmium, as well as zinc and copper, but were apparently protected from the deleterious effects of high metal body burdens by metallothioneins. Amounts... 

When animals are fed experimental diets lacking copper or zinc, their copper or zinc status rapidly declines, suggesting that there is not a storage pool of these metals. Thus, while the small, cysteine-rich protein metallothionein (see below) can avidly bind zinc and copper, this may reflect its role in detoxification rather than as a specific storage form. This is reflected by the fact that metallothionein genes are typically expressed at a basal level, but their transcription is strongly induced by heavy metal load. 

Zinc (Zn) deficiency is teratogenic in rats, and fetal skeletal defects are prominent. Embryofetal zinc deficiency secondary to changes induced by substances in maternal Zn metabolism is a well-established mechanism for developmental toxicity (29-31). Several substances, including urethane and alpha-hederin cause similar malformations as Zn deficiency in rodents. A number of mechanistic studies have shown that these substances act via an acute-phase reaction induction of metallothionein in the maternal liver which binds systemically available Zn in the pregnant animal. This results in a systemic redistribution of Zn. As a consequence the substances produce a transient but developmentally adverse Zn deficiency in the... 

The binding of cadmium to metallothionein decreases toxicity to the testes but increases the nephrotoxicity, possibly because the complex is preferentially, and more easily, taken up by the kidney than the free metal. Dosing animals with the cadmium-metallothionein complex leads to acute kidney damage, whereas exposure to single doses of cadmium itself does not. 

If animals ingest excessive amounts of Zn(n), Cd (II), Hg(II), or Cu(I) their livers and kidneys accumulate these metals as complexes of proteins called metallo-thioneins/1 e In mammals at least three related genes encode these metal-binding proteins. The best known, metallothionein II, has a highly conserved 61-residue sequence containing 20 cysteine residues and no aromatic residues. 

Since zinc ions have no color their presence has often been overlooked. Zinc ions will doubtless be found in many more places within cells. Zinc is usually the major component of the bound metals in the metallothioneins (Box 6-E). These small 6.6-kDa proteins which contain 33% cysteine and bind as many as six ions of Cd2+, Hg2+, Cu2+, or Zn2+ per molecule are present in all animal tissues as well as in plants and some bacteria.)... 

We have seen (Section 56.1.13.2.2) that cadmium can induce the synthesis of a Cd-binding protein in fact, the administration of copper, zinc, cadmium or mercury to animals induces the synthesis of these proteins called metallothioneins, which play an important role in the metabolism of these elements. 

The addition of copper, zinc, cadmium or mercury to animals results in the synthesis of a cysteine-rich protein called metallothionein.1147-1149 These proteins have been isolated from a number of sources, and have molecular weights in the range 6000 to 12 000 with a cysteine content of about 30-35% of the total amino acid content. They have also been found in microorganisms and plants. These proteins are thought to play an important role in the storage of zinc and copper, and as a result of their storage capacity, are able to bind and detoxify cadmium and mercury. 

A kind of hyposensitivity is that induced by repeated exposures to a toxic substance leading to tolerance and reduced toxicides from later exposures. Tolerance can be due to a less toxic substance reaching a receptor or to tissue building up a resistance to the effects of the toxic substance. An example of the former occurs with repeated doses of toxic heavy metal cadmium. Animals respond by generating larger quantities of polypeptide metallothionein, which is rich in -SH groups that bind with Cd2+ ion, making it less available to receptors. 

Metallothionein has been isolated from virtually all of the major mammal organs, including liver, kidney, brain, heart, intestine, lung, skin, and spleen. Nonlethal doses of cadmium, mercury, and lead induce synthesis of metallothionein. In test animals, nonlethal doses of cadmium followed by an increased level of metallothionein in the body have allowed later administration of doses of cadmium at a level fatal to nonacclimated animals, but without fatalities in the test subjects. 

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