Mechanisms of hepatic methylmercury uptake

Journal Article · Wed Nov 01 04:00:00 EST 1995 · Journal of Toxicology and Environmental Health

DOI:https://doi.org/10.1080/15287399509532040· OSTI ID:387352

Ballatori, N; Truong, A T ^[1]

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1. Univ. of Rochester School of Medicine, NY (United States)

The mechanism by which methylmercury is cleared from hepatic portal blood was examined in isolated rat livers perfused single-pass with Krebs-Henseleit buffer. [{sup 203}Hg]Methylmercury (0.24-24 {mu}M) was infused over a 30-min interval, followed by a 30-min washout, as a complex with the endogenous ligands L-cysteine (CH{sub 3}Hg-L-cys), gluthathione (CH{sub 3}Hg-DTT), chloride (CH{sub 3}HgCl), and the D-enantiomer of cysteine (CH{sub 3}Hg-D-cys). The sulfhydryl-containing compounds were added at a 10-fold molar excess. When administered as the albumin complex, only a small fraction of the [{sup 203}Hg]methylmercury was cleared from perfusate ({approximately}8%) and excreted into bile (0.7%). Hepatic uptake and biliary excretion of methylmercury was considerably higher for the other complexes. For the dithiothreitol complex, hepatic extraction of methylmercury was nearly complete during single-pass perfusion. A comparison of hepatic removal of increasing doses of CH{sub 3}Hg-L-cys and CH{sub 3}Hg-L-cys and CH{sub 3}-D-cys revealed little difference. Moreover, the fraction of methylmercury removed was similar at concentrations of 0.24, 2.4, and 24 {mu}M, indicating no saturability of uptake in this dose range. Methylmercury was not hepatotoxic at concentrations up to 24 {mu}M if administered as a mercaptide; however, the chloride complex (CH{sub 3}HgCl) produced cholestasis and an increase in perfusion pressure at a concentration of only 0.24 {mu}m. These findings indicate that hepatic methylmercury uptake and toxicity are dependent on the chemical form in blood plasma. Uptake was faster when methylmercury was present as a cysteine or glutathione complex, as compared to the albumin complex; however, the lack of steroselectivity indicates that the uptake process may be relatively unselective.

• Sponsoring Organization: USDOE
• OSTI ID: 387352
• Journal Information: Journal of Toxicology and Environmental Health, Journal Name: Journal of Toxicology and Environmental Health Journal Issue: 3 Vol. 46; ISSN JTEHD6; ISSN 0098-4108
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
56 BIOLOGY AND MEDICINE
APPLIED STUDIES
BIOCHEMISTRY
BIOLOGICAL PATHWAYS
LIVER
METHYLMERCURY
UPTAKE