Selenium - Toxicology of Metals - page 785

7.7.7 Mercury The brain levels of mercury were remarkably high, up

to 13 g/g. Analysis of biopsy specimens from skin

pigmentations found in mercury-exposed workers
revealed deposits containing mercury and selenium
(Kennedy et al ., 1977). Contrary to a previous fi nding,
workers exposed to elemental mercury vapor seem to
excrete signifi cantly more selenium in urine than unex-
posed controls (Alexander et al ., 1983).

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7.7.7.1 Inorganic Mercury Compounds
Inorganic mercury exposure occurs with two forms of
the element: mercury salts (Hg 2+ ) and elemental mercury
(Hg 0 ). The kidney is the critical organ for Hg 2+ , whereas
the CNS is the critical organ for Hg 0 . Mercury vapor is
probably dissolved in the blood after uptake and is trans-
ported into the brain where it is oxidized to Hg 2+ .
When selenite is coadministered or given shortly
after mercuric mercury, it effectively protects against
acute tubular necrosis, damage of the kidney, and
death. However, repeated simultaneous administra-
tion of mercuric chloride with selenite resulted only
in partial protection of the kidney damage caused by
mercury (Chmielnicka et al ., 1978). Mercuric admin-
istration inhibited GSH metabolizing enzymes and
GSHPx in the kidney. This effect was reversed by
selenite administration (Chung et al ., 1982). Coadmin-
istration of the two elements usually leads to increased
whole-body retention of both elements and especially
of mercury. Both renal and fecal excretion of mercury
are reduced, and changes in the organ distribution
are seen (Hansen et al ., 1981; Kristensen and Hansen,
1979; Magos and Webb, 1980). When mercury and
selenium are coadministered, selenium and mercury
form a high-molecular-weight complex with a plasma
protein, thereby reducing Hg in target organs such as
the kidney. High-molecular-weight complexes of Hg
and Se are also seen in other organs. The protein in
plasma is selenoprotein P (Yoneda and Suzuki, 1997).
Timing of Hg and Se exposure seems to be critical,
because only exposure hours apart strongly reduces
the protective effect of selenium (Magos and Webb,
1980; Watanabe, 2002). Mercuric chloride decreases
the toxic effects of selenium and reduces the forma-
tion of methylated selenium metabolites, probably by
forming complexes with selenide, and potentiates the
toxicity of methylated selenium compounds (Levander
and Argrett, 1969; Magos and Webb, 1980).
It is not known whether the toxic effects of mercury
vapor on the CNS are infl uenced by selenite. Toxi-
cokinetic studies with Hg 0 and selenium have been
performed on rats and mice. Experiments on mice
showed that selenite pretreatment did not change the
immediate uptake and distribution of mercury but
markedly increased the retention in the whole body
and especially in the lungs (Hansen et al ., 1981; Khayat
and Dencker, 1983). In rats, mercury retention tended to
be elevated in liver and serum (Nygaard and Hansen,
1978). In retired miners previously exposed to elemen-
tal mercury, Kosta et al . (1975) found a coaccumulation
of mercury and selenium in molar ratio close to unity
in the kidneys, the pituitary, the brain, and the thyroid.

7.7.7.2 Organic Mercury Compounds
Organic mercury compounds usually include alkyl
mercurials, methoxyethylmercury, and phenylmercury.
The latter two compounds have seldom been studied
with respect to toxicity and interaction with selenium.
Of the alkylmercury compounds, most work has been
done with methylmercury, which has also been most
extensively studied with respect to its interaction
with selenium (Ganther, 1980; Magos and Webb, 1980;
Skerfving, 1978). Methylmercury selectively damages
the nervous system in man, leading to ataxia, dysar-
thria, constriction of the visual fi eld, and paresthesias.
The protective effect of selenium against methylmer-
cury toxicity was fi rst reported by Ganther et al . (1972).
Later, such protection was found in chick, quail, rat,
mice, and cat (Ganther, 1980; Magos and Webb, 1980;
Skerfving, 1978). When methylmercury is given in a
single dose or in a limited number of doses, selenite
effectively prevents the onset of neurological disor-
ders. During long-term dosing with methylmercury,
selenium offers some protection and at least delays
the onset of symptoms (Chang, 1983; Magos and
Webb, 1980). Remarkably small amounts of selenite
are required to provide a protective effect even in
cell cultures (Alexander et al ., 1979; Ganther, 1980).
The protective effects occur even if coadministration
of selenium leads to heightened levels of mercury
in brain (Alexander and Norseth, 1979; Chen et al .,
1975; Ganther, 1980; Magos and Webb, 1980). How-
ever, decreased brain levels have also been reported
(Komsta-Szumska and Miller, 1984). The elimina-
tion of mercury after several doses of methylmer-
cury can be described by a one-compartment model
(half-time, 23.6 days). Coadministration of several
doses of selenite and methylmercury revealed a two-
compartment model for elimination of mercury (half-
time, 8.7 and 40.8 days) (Komsta-Szumska and Miller,
1984). The formation of a lipophilic (CH 3 Hg) 2 Se com-
plex, probably easily penetrating the blood-brain bar-
rier, has been reported to take place both in vitro and
in vivo (Magos and Webb, 1980; Masukawa et al ., 1982;
Naganuma and Imura, 1980). Reduced biliary excre-
tion of MeHg is a prominent effect of selenium com-
pounds, and, concomitantly, an increase in exhalable
methylated selenium metabolites is observed. It has