Tissue Accumulation and Excretion

Chan et al. (1992) have examined the relative renal toxicity of Hg in rats when Hg is administered as either HgCl2 or the complex with metal-lothionein (MT). They observed that the injury caused by Hg-MT localized mainly in the terminal portions of the proximal convoluted tubule and the initial portions of the proximal straight tubule, whereas HgCl2 caused necro- 

The rate of biliary excretion of Hg is very low in comparison with methylmercury excretion (Ballatori and Clarkson 1984b). The form of Hg2+ excreted into the bile has been identified as a complex with GSH (GSHgSG) (Ballatori and Clarkson 1984b). Inhibition of biliary secretion of GSH by administration of sulfobromophthalein (BSP) resulted in a parallel inhibition of Hg secretion (Ballatori and Clarkson 1984a). Thus, the biliary secretion of Hg may be in large part dependent on the biliary transport of GSH. The mechanism of urinary excretion of Hg has not yet been clarified. As described above, Hg is incorporated into the kidneys by a y-GTP-dependent system, and inhibition of y-GTP significantly increases urinary excretion of Hg (Tanaka et al. 1990). Therefore, GSHgSG which has escaped from the action of y-GTP may be excreted into the urine. 

Since mercuric mercury mainly accumulates in the kidney, Hg causes severe nephrophathy, characterized by extensive loss of proximal tubule function and viability (Ganote et al. 1975). The renal toxicity of Hg can be estimated by increases in urinary levels of biomarker enzymes, such as lactate dehydrogenase, alkaline phosphatase, aspartate aminotransferase, and y-glutamyltranspeptidase. Among these marker enzymes, alkaline phosphatase and aspartate aminotransferase are the most sensitive indicators, and lactate dehydrogenase is the most responsive marker to renal mercury toxicity (Dieter et al. 1992). 

Glomerular injury is also observed in the kidney of rat after a single high-dose administration of HgCl2. However, the magnitude of the injury 

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