revised final - Agency for Toxic Substances and Disease Registry ...

MERCURY 323
2. HEALTH EFFECTS
2.8 INTERACTIONS WITH OTHER CHEMICALS
As with many other metals, both toxic and nontoxic, interrelationships exist that can influence and alter the
absorption, distribution, excretion, and toxicity of one or more of the component metals. For example, the
zinc status of an individual can affect mercury toxicity. Pretreatment with zinc provides some protection
from the nephrotoxic effects of inorganic mercury in rats (Zalups and Cherian 1992). The data indicate
that zinc-induced metallothionein binds mercury in the renal cortex and shifts the distribution of mercury
from its site of toxicity at the epithelial cells of the proximal tubules. Thus, the renal content of mercury is
increased, yet less is available to cause toxicity. In contrast, the renal toxicity of mercuric chloride is
exacerbated in zinc-deficient animals (Fukino et al. 1992). In the zinc-deficient state, less mercury
accumulates in the kidneys, but the toxicity is greater. The mechanism of the protection appears to involve
more than simply a redistribution of renal mercury, because in the absence of mercury exposure, zinc
deficiency increases renal oxidative stress (increased lipid peroxidation, decreased reduced ascorbate).
When mercury exposure occurs, the oxidative stress is compounded (increased lipid peroxidation and
decreased glutathione and glutathione peroxidase). Thus, zinc appears to affect the biochemical protective
mechanisms in the kidneys as well.
Similarly, in most studies, the simultaneous administration of mercury and selenium in equimolar doses to
animals has resulted in decreased toxicity of both elements in acute and chronic exposure studies. This
effect has been observed with inorganic and organic mercury and with either inorganic or organic
selenium compounds, although inorganic forms of selenium appear to be more effective than organic
forms (Chang 1983; Skerfving 1978). Selenium protects against the acute nephrotoxicity of the mercuric
ion and the methylmercuric ion in rats (Ganther 1980; Ganther et al. 1972; Hansen 1988; Magos et al.
1987; Parizek and Ostadolva 1967) and possibly against acute neurotoxicity of methylmercuric ion in rats
(Ohi et al. 1980). The protective effect of selenium has been associated with a higher whole-body
retention of mercury rather than with increased mercury excretion (Hansen 1988; Magos et al. 1987).
Mercury-selenium complexes are formed when these chemicals are co-administered. Mercuric mercury
forms a complex with selenium and a high-molecular weight protein (Naganuma and Imura 1981).
Methylmercury forms a bismethyl-mercury selenide complex. Although the specific mechanism for the
protection is not well understood, possible mechanisms for selenium's protective effect include
redistribution of mercury (Mengel and Karlog 1980), competition by selenium for mercury-binding sites
associated with toxicity, formation of a mercury-selenium complex that diverts mercury from sensitive
targets (Hansen 1988; Magos et al. 1987; Naganuma and Imura 1981), and prevention of oxidative damage by increasing