||Altered Zn Status by alpha-Hederin in the Pregnant Rat and Its Relationship to Adverse Developmental Outcome.
Daston, G. P. ;
Overmann, G. J. ;
Baines, D. ;
Taubeneck, M. W. ;
Lehman-McKeeman, L. D. ;
||Health Effects Research Lab., Research Triangle Park, NC. Developmental Toxicology Div. ;Procter and Gamble Co., Cincinnati, OH. Miami Valley Labs. ;California Univ., Davis.;National Institutes of Health, Bethesda, MD.
Animal pregnancy ;
Embryo development ;
Tissue distribution ;
In vitro analysis ;
Dose-response relationships ;
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||The hypothesis that hepatic metallothionein (MT) induction in the pregnant animal results in a Zn deficiency in the embryo was tested by treating pregnant rats with alpha-hederin, reported to induce MT in rat liver. Morphological development was assessed in term fetuses. A single dose of alpha-hederin, of 3-300 micromoles/kg, caused a dosage-related increase in maternal hepatic MT. Maximum induction was 11-15-fold greater than control and occurred at dosages of 30 micromoles/kg and higher. (Zn) concentration in liver and liver cytosol increased along with MT, reaching a maximum at dosages of 30 micromoles/kg and higher. Plasma (Zn) decreased after alpha-hederin treatment to a level approximately 75% of control at 30 micromoles/kg and 50% of control at 300 micromoles/kg. Zn distribution was evaluated by giving a (65)Zn 8 hours after treatment and measuring (65)Zn 10 hr later. Both 30 and 300 micromoles/kg increased resorptions, and 300 micromoles/kg decreased fetal weight and increased the incidence of abnormal fetuses. These data support the hypothesis that systemic changes in Zn status, brought about by induction of hepatic MT, may be a mechanism for maternally-mediated abnormal development.
||Pub. in Reproductive Toxicology, v8 n1 p15-24 Feb 94. Prepared in cooperation with Procter and Gamble Co., Cincinnati, OH. Miami Valley Labs. and California Univ., Davis. Sponsored by National Institutes of Health, Bethesda, MD.
||%AUT:J. M. /Rogers ;C. L. /Keen
|NTIS Title Notes
||Reprint: Altered Zn Status by alpha-Hederin in the Pregnant Rat and Its Relationship to Adverse Developmental Outcome.
||PC A03/MF A01