Toxic metal excretion

Not all agents can be readily metabolized. The toxic metals lead and mercury are elements that cannot be degraded but must still be removed from the body. Another important mechanism of detoxification is the attachment or binding of another compound to a toxic chemical to make it easier for the kidney to filter the compound out of the blood and excrete it in the urine. A primary purpose of the kidney is to screen the blood for waste products and concentrate them in the urine for excretion, as occurs, for example, with mercury. Caffeine is excreted in the urine at approximately the same concentration as the blood because the kidney cannot concentrate caffeine. Vitamins, however, are readily concentrated and excess quickly eliminated in the urine. 

The results of studies on animals show that cadmium is an extremely toxic metal. Cadmium is poorly excreted by the human body and although only 5-10% of that ingested is absorbed, it does accumulate in the body over time with renal damage being caused by long-term exposure.14 One sign of this damage is proteinuria (the appearance of increased levels of unaltered proteins in the... 

In most cases, the capacity of chelating agents to prevent or reduce the adverse effects of toxic metals appears to be greatest when they are administered very soon after an acute metal exposure. Use of chelating agents days to weeks after an acute metal exposure ends—or their use in the treatment of chronic metal intoxication—may still be associated with increased metal excretion. However, at that point, the capacity of such enhanced excretion to mitigate the pathologic effect of the metal exposure may be reduced. 

R. Albert, Accumulation of toxic metals with special reference to their absorption, excretion and biological half times. Environ. Physiol. Biochem. 3 65, 1978. 

Desferrioxamine B has also found therapeutic application for various pathological conditions due to aluminum overload. Accumulation of this toxic metal is frequently observed in chronically dialyzed patients who have lost the abihty to clear via renal excretion. Desferrioxamine B has also been recommended for the diagnosis of such an overload state. 

Analysis of urine samples for metals content is a useful way to study the presence of toxic metals in humans. The metal content can give an indication of the performance of kidneys in regulating the body electrolyte, water metabolism and rate of excretion of metals from the body. ICP-OES can be used to measure the level of heavy metals in urine of both healthy and pathological cases. Sample preparation for analysis of these samples must involve an acid digestion in a microwave oven or bomb combustion to destroy the interfering organics present. Metals such as Pb, Cd, Tl, Se, Sn and Hg are the usual metals requiring analysis. 

The concentration of (EDTA) ", and thus the ability to complex metal ions, will depend upon the pH. A decrease in pH results in an increase in the deprotonation of EDTA and hence an increase in the concentration of the ED I A ion. The effect of this is that only metal ions with a very high affinity for EDTA will be able to form stable complexes. The stability constants for the EDTA and [diethylenetriaminepentaacetic acid] - (DTPA ) complexes with some important metal ions that are of particular interest for chelation therapy are listed in Table 7.3. It is important to note that the stability of the EDTA and DTPA complexes with toxic metals, such as lead, mercury, cadmium, or plutonium are quite similar to those with essential metals such as zinc, cobalt or copper however, the Ca complex is many orders of magnitude lower. This has important implications for chelation therapy. First, the mobilization and excretion of zinc and other essential metals are likely to be increased, along with that of the toxic metal during EDTA treatment and secondly, the chelation of the ionic calcium in the blood, that can cause tetany and even death, can be avoided by administering the chelator as the calcium salt. 

Fomina, M., Hillier, S., Chamock, J. M., Melville, K., Alexander, I. J., and Gadd, G. M. (2005b). Role of oxalic acid over-excretion in toxic metal mineral transformations by Beauveria caledonica. Appl. Environ. Microbiol. 71, 371—381. 

The kidney plays a key roll in the absorption of mercury in the body. Kidney tissue contains a thiol-rich protein called metaUothionein. Exposure of the kidney to mercury and other toxic metals causes production of this protein which binds the metals tightly, and retains it in the kidney in a relatively harmless form. As long as the kidney is not overwhelmed by the influx of the toxic metal, the excretion of mercury will eventually balance intake so that worsening of adverse symptoms will be limited. However, acute levels can lead to renal failure. 

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