Abstract
A two-fold difference in elimination rates of methylmercury (MM) between two genetic variant strains of mice was due to a five-fold greater rate of urinary excretion in the fast-excreting strain. Further investigation indicated that the difference could not be accounted for by biotransformation of MM to the inorganic form. However, several factors that could conceivably influence MM renal excretion were altered, including an increased plasma total glutathione (GS) concentration, and an increased rate of output of GS in the urine. To assess the role that GS may play in the elimination of methylmercury in the urine, the γ-GTP inhibitor, L-[αs,5s]-α-Amino-3-chloro-4,5-Dihydro-5-Isoxazoleacetic Acid (AT-125), was administered to CBA/J mice previously treated with 203Hg-MM to determine whether increasing urinary GS could result in a simultaneous increase in urinary excretion of MM. Increasing doses of AT-125 resulted in a dose-dependent increase in urinary GS. MM excretion, however, did not increase in a direct proportion to increasing concentrations of GS.
Earlier studies in whole blood indicated that millimolar plasma concentrations of low molecular weight thiols were required to redistribute MM from cellular binding sites into plasma. Similarly, increased urinary MM excretion coincided only with the period following AT-125 administration when urinary thiol was elevated to 300 to 500 times normal levels to the millimolar concentration range. These studies suggest that changes in GS elimination into urine may only be of consequence with regard to MM excretion once GS levels have been elevated to the millimolar concentration range.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
Similar content being viewed by others
References
Al-Abbasi, A. H., Kostyniak, P. J., and Clarkson, T. W., 1978, An extracorporeal complexing hemodialysis system for the treatment of methylmercury poisoning. III. Clinical applications. J. Pharmacol. Exp. Then 207:249–254.
Aleo, M., Taub, M. L., Nickerson, P. A., and Kostyniak, P. J., 1989, Primary cultures of rabbit renal proximal tubule cells: I. Growth and Biochemical Characteristics. In Vitro 25:776–783.
Aleo, M. D., Taub, M. L. and Kostyniak, P. J., 1990, Primary cultures of rabbit renal proximal tubule cells: Selected Phase I and Phase II Metabolic Capacities. In Vitro 4:6727–773.
Kostyniak, P. J., Clarkson, T. W., Cestero, R.V., Freeman, R. B. and Al-Abbasi, A. H., 1975, An extracorporeal complexing hemodialysis system for the treatment of methylmercury poisoning. I. In vitro studies of the effects of four complexing agents in the distribution and dialyzability of methylmercury in human blood. J. Pharmacol. Exp. Ther. 192:260–269.
Kostyniak, P. J., Clarkson, T. W., and Al-Abbasi, A. H., 1977, An extracorporeal complexing hemodialysis system for treatment of methylmercury poisoning. II. In vivo applications in the dog. J. Pharmacol. Exp. Ther. 203:253–263.
Kostyniak, P. J., 1980. Differences in elimination rates of methylmercury between two genetic variant strains of mice. Toxicol. 6:405–410.
Kostyniak, P. J., 1983, Methylmercury removal in the dog during infusion of 2,3-dimercapto-succinic acid. J. Toxicol. Environ. Health 11:947–957.
Mulder, K. M., 1985, Investigation of the mechanism of a strain variation in renal elimination of methylmercury in mice. PhD Thesis, University of Buffalo.
Mulder, K. M., and Kostyniak, P. J., 1985a, Stabilization of glutathione in urine and plasma: Relevance to urinary metal excretion studies. J. Anal. Toxicol. 9, 31–35.
Mulder, K. M., and Kostyniak, P. J., 1985b, Effect of L-(αS,5S)-a-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid on urinary excretion of methylmercury in the mouse. J.Pharmacol. Exp. Ther. 234:156–160.
Mulder, K. M. and Kostyniak, P. J., 1985c, Involvement of glutathione in the enhanced renal excretion of methylmercury in CFW Swiss mice. Toxicol. Appl. Pharmacol. 78:451–457.
Norseth, T., 1971, Biotransformation of methyl mercuric salts in the mouse studies by specific determination of inorganic mercury. Acta. Pharmacol. et Toxicol. 29:375–384.
Norseth, T. and Clarkson, T. W., 1971, Intestinal Transport of 203Hg-Labeled Methyl Mercury Chloride: Role of biotransformation in rats. Arch. Envir. Health 22:568–577.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1991 Springer Science+Business Media New York
About this chapter
Cite this chapter
Kostyniak, P.J. (1991). Mechanisms of Urinary Excretion of Methylmercury (MM). In: Suzuki, T., Imura, N., Clarkson, T.W. (eds) Advances in Mercury Toxicology. Rochester Series on Environmental Toxicity. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-9071-9_5
Download citation
DOI: https://doi.org/10.1007/978-1-4757-9071-9_5
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4757-9073-3
Online ISBN: 978-1-4757-9071-9
eBook Packages: Springer Book Archive