Abstract
The primary aim of the present study was to evaluate the effects of different means of depleting glutathione (GSH) in the kidneys and liver on the renal and hepatic accumulation and disposition of a nontoxic dose of inorganic mercury. Renal and hepatic disposition of mercury were evaluated 1 hr after the intravenous administration of a 0.5 μmol/kg dose of mercuric chloride in control rats and rats pretreated with acivicin, buthionine sulfoximine (BSO), or diethylmaleate (DEM). Pretreatment with acivicin or DEM caused significant decreases in the net renal accumulation of mercury during the first hour after the injection of mercuric chloride. The primary effects of these two pretreatments occurred in the renal cortex, although pretreatment with DEM also caused significant decreases in the concentration of mercury in the outer stripe of the outer medulla. Despite the fact that pretreatment with BSO caused a reduction in the renal content of GSH, comparable with that caused by DEM, pretreatment with BSO had no significant effect on the renal disposition of mercury. Pretreatment with acivicin, BSO, or DEM also caused significant decreases in measurable reduced GSH, with BSO and DEM having the most pronounced effects. Injection of the nontoxic dose of mercuric chloride after pretreatment with acivicin resulted in slightly, but significantly, decreased hepatic content of mercury. Interestingly, pretreatment with BSO or DEM actually caused significant increases in the hepatic content of mercury 1 hr after the injection of mercuric chloride. We postulate that this effect was due to a diminished ability of hepatocytes to export mercuric conjugates of GSH out into either the bile or blood. The results of this study indicate that depletion of renal GSH by conjugation reactions between GSH and DEM leads to an acute reduction in the renal accumulation of inorganic mercury. However, the results also indicate that depletion of renal levels of GSH by inhibition of GSH synthesis does not affect acutely the ability of the kidneys to accumulate inorganic mercury. Thus, it seems that factors in addition to intracellular GSH status play an important role in the renal accumulation/retention of inorganic mercury.
Footnotes
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Send reprint requests to: Dr. Rudolfs K. Zalups, Division of Basic Medical Sciences, Mercer University School of Medicine, 1550 College Street, Macon, GA 31207.
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This study was supported in part by grants from the National Institutes of Health (ES05157 and DK40725).
- Abbreviations used are::
- GSH
- glutathione
- BSO
- buthionine sulfoximine
- DEM
- diethylmaleate
- GSSG
- glutathione disulfide
- Received November 26, 1996.
- Accepted January 24, 1997.
- The American Society for Pharmacology and Experimental Therapeutics
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