Acute phase response-induced alterations in maternal and conceptus nutrient metabolism

3 ACUTE PHASE RESPONSE-INDUCED ALTERATIONS IN MATERNAL AND CONCEPTUS NUTRIENT METABOLISM 

The acute phase response protein, metallothionein, MT, belongs to a family of low molecttlar weight cysteine-rich proteins that can bind nutritionally important bivalent cations such as zinc and copper, as well as the envirorunental toxicants, cadmittm and mer-ctuy. Two of the MT proteins (MT-1 and MT-2) are widely expressed in the body with highest concentrations in the liver, kidney, intestine and pancreas. The MT-3 isoform is predominantly foimd in brain while expression of the MT-4 isoform has been detected in skin and tongue squamous epithelium and maternal deciduttm. Postulated functions of MT include protection against heavy metal toxicity, as a contributor to zinc homeostasis and metabolism, and as an antioxidant and flee radical scavenger. 

Health and Safety Issues with Plasticizers and Plasticized Materials 

In this scenario, as a consequence of the maternal acute phase response, there is a marked increase in the synthetic rates of several proteins including MT in maternal liver. The increase in the concentration of MT results in a sequestration of zinc in maternal liver, a drop in plasma zinc, and reduced zinc transfer to the embryo. If the decreased zinc transfer to the embryo occius ditring critical periods of organogenesis, zinc-dependent processes can be disrupted in the growing embryo leading to developmental defects and malformatiorts.  

Numeroits diverse compoimds have been shown to mediate developmental toxicity by altering maternal and embryo/fetal zinc metabolism. For example, the saponin, a-hed-erirt, which is a component of oriental herbs used to treat hepatitis and infectious diseases, has been shown to induce maternal liver MT and zinc concentrations and result in decreased embryonic zinc, and increased malformations. Using an oral dose of the radioactive isotope Zn, Duffy and coworkers showed that the tissue distribution of Zn reflected the increase in hepatic MT. When rat embryos were cirltured in serum taken from rats two hours after a-hederin treatment (e.g. before the increase in maternal hver MT production), embryo development was normal. In contrast, embryos cultured in serum taken from rats 18 hours after a-hederin treatment (e.g., peak MT production) developed multiple abnormalities. The addition of zinc to the 18-hoirr post-a-hederin treated serum resulted in normal embryonic development indicating that the low zinc content of the serum was directly responsible for the a-hederin-induced teratogenicity. 

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