Chemistry Reference
In-Depth Information
Fowler and Silbergeld; 1989), because they may infl u-
ence target molecular and cellular responses to mix-
tures of gallium and arsenic or indium and arsenic
(Conner
et al.
, 1994).
that exposure to small amounts of cadmium may cause
a redistribution of zinc in the organism (Petering
et al.
,
1971). Zinc concentrations increase in liver and kidney
and might decrease in other organs where cadmium
does not accumulate to the same extent (e.g., in the tes-
tes). It has also been shown that if pregnant animals are
exposed to cadmium, the fetal concentrations of zinc
and of copper may become lower (Pond and Walker,
1975). Cadmium, a potent inhibitor of iron uptake in
mice fed a low iron diet, impaired zinc uptake under
these conditions (Hamilton
et al.
, 1978). Such interac-
tions infl uencing the fetal levels of essential elements
may be important components for the explanation of
the effects of low-level Cd exposures on the fetal brain
(cf Chapter 23).
In rats, cadmium (Cd2+) and chromium (Cr3+)
inhibited zinc (Zn2+) uptake, but chromium (Cr6+) did
not show any affi nity for the transport process (Lyall
et
al.
, 1979). In animals exposed to cadmium over a long
period of time, there is a marked accumulation of cad-
mium in the liver and kidneys; in addition, there is
an increase in zinc and a decrease in iron in these
organs, whereas the concentration of copper is usu-
ally unchanged (Sugawara, 1984). It could be expected
that cadmium would cause changes in the activities of
some enzymes that require zinc. It has been shown that
the renal activity of leucine aminopeptidase, which is a
zinc-requiring enzyme, is reduced in animals exposed
to cadmium (Cousins
et al.
, 1973).
It is known from animal experiments that the die-
tary intake of iron, zinc, and calcium is of importance
for the gastrointestinal uptake of Cd (see reviews by
Andersen
et al.
[2004] and Chaney
et al.
[2004]).
There are indications that contributing factors for
Itai-Itai disease were low intakes of calcium and other
minerals, vitamin D, and protein. The poor nutritional
conditions in many areas of Japan during World War
II were discussed and a comparison between diets in
the endemic region of Itai- , Toyama prefecture, Japan
as a whole and Sweden was presented by Kjellstrom in
1986. Lower dietary intakes calcium and of fat-soluble
vitamins compared with Sweden and the practice by
women in the endemic area of wearing clothes covering
their whole body, including hands and face, may have
provided only marginally adequate calcium intake and
marginal or less than marginal vitamin D activity. Such
conditions most probably made this population more
sensitive to the development of bone effects of Cd than
populations in other countries (Kjellstrom, 1986; Nord-
berg, 1974). Although it is clear that the high cadmium
intake in the endemic area was the main causal factor
for development of the disease (cf Chapter 23), these
other factors may have contributed to the development
of severe osteomalacia and osteoporosis with many
4.2 Interactions Between Cadmium and
Other Metals
Many studies show that zinc can counteract toxic
effects of cadmium. Cadmium and zinc belong to the
same group of the Periodic Table. It has been specu-
lated that cadmium can displace or replace zinc in
some essential systems in the organism, thus causing
functional changes. Metallothionein, a low-molecular-
weight cysteine-rich protein, can bind cadmium, cop-
per, and zinc; and this protein will bind most of the
cadmium stored and kidneys, being inert in this form
and preventing cadmium ions from interfering with
the essential metals. Some parts of the reproductive
system have particularly high concentrations of zinc,
which is of great functional importance. Lethal toxic-
ity from injection of Cd compounds can be protected
by pretreatment by Zn or Cd (Leber and Miya 1977;
Nordberg, 1972). The induction of MT by the pretreat-
ment, shown to take place in the liver, most probably
is the explanation for such protective effects. Studies
using MT transgenic and MT null mice have demon-
strated lower lethality and lower liver toxicity from Cd
in mice expressing increased levels of MT (Liu
et al.
,
1995) and increased such toxicity in MT-null mice (Liu
et al.
, 1998). Cadmium in single doses may cause tes-
ticular destruction, but this damage may be prevented
by injection of large amounts of zinc (Parizek, 1957),
selenium, or even pretreatment with smaller doses of
cadmium. The latter phenomenon is likely to be due
to the induction of a small cadmium-binding protein
(Nordberg, 1971) protecting against the deleterious
effect of the large dose. Although it has been speculated
that this protein might be metallothionein, the fact that
various strains of mice with variable susceptibility to
this effect are not related to MT, makes it likely that
the protective protein is different from metallothionein
(see Section 3.2 of this chapter). Gunnarsson
et al.
(2004)
showed that pretreatment with zinc protected against
Cd-induced testicular prostaglandin increase, a prob-
able mechanism by which Cd inhibits testosterone syn-
thesis. In many studies on the relationships between
zinc and cadmium, animals exposed to cadmium were
given diets with extremely high concentrations of zinc,
which might have prevented some of the expected
effects of cadmium. Of greater interest are the studies in
which animals have been exposed to cadmium, but the
dietary concentrations of zinc have been just adequate
or suboptimal. In such experiments, it has been shown
