Distribution of mercury 203 in pregnant rats and their fetuses following systemic infusions with thiol-containing amino acids and glutathione during late gestation.
To investigate the effect of amino acids and the tripeptide glutathione (GSH) on tissue uptake of methylmercury (MeHg) in the developing rat fetus in utero, pregnant rats were continuously infused into the external jugular vein with 0.1 mM L-cysteine, 0.1 mM L-leucine, 0.1 mM GSH or saline commencing on day 17 of gestation. This was followed at 24, 48, and 72 hours by external jugular infusion of 50 microM [203Hg]-MeHgCl administered in 1 ml over 1 hour. Pups were surgically removed from the uterus on gestational day 21. Whole body, brain, kidney, liver, and placental 203Hg radioactivity was measured by means of gamma-spectrometry. Brain 203Hg concentration in pups exposed in utero to L-cysteine was significantly higher compared with pups exposed to saline (P less than 0.05). Brain 203Hg concentration in pups exposed in utero to L-leucine and GSH was significantly depressed compared with pups exposed to saline (P less than 0.05). Kidney 203Hg concentration was not significantly changed in all treatment groups compared with controls. Liver 203Hg concentration was significantly depressed in L-leucine- and GSH-treated pups compared with controls (P less than 0.05). Placental 203Hg concentration was not affected by any treatment compared with controls. These effects occurred despite no difference in total 203Hg body burden among pups, irrespective of the treatment. In addition, infusion with L-cysteine resulted in a significant increase in 203Hg brain concentration in dams compared with controls, and 203Hg brain concentration in L-leucine- and GSH-treated dams was significantly depressed compared with controls. Thus 203Hg distribution in both adult and developing animals is altered by chronic amino acid or GSH infusions and suggests that MeHg uptake may be mediated through the formation of a cysteine-MeHg complex which is transported across the blood-brain barrier by the neutral amino acid carrier transport system.
Aschner
M
M
Division of Toxicology, School of Medicine and Dentistry, University of Rochester, New York 14642.
Clarkson
T W
TW
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D003545:Cysteine / Q000494:pharmacology*; D005260:Female; D005865:Gestational Age; D005978:Glutathione / Q000494:pharmacology*; D007262:Infusions, Intravenous; D007668:Kidney / Q000032:analysis / Q000187:drug effects; D007930:Leucine / Q000494:pharmacology*; D008099:Liver / Q000032:analysis / Q000187:drug effects; D008431:Maternal-Fetal Exchange; D008767:Methylmercury Compounds / Q000493:pharmacokinetics* / Q000633:toxicity; D010920:Placenta / Q000032:analysis / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D013438:Sulfhydryl Compounds / Q000494:pharmacology*; D014018:Tissue Distribution
D008767:Methylmercury Compounds; D013438:Sulfhydryl Compounds; D005978:Glutathione; D007930:Leucine; D003545:Cysteine