Chemistry Reference
In-Depth Information
1985; Kagi
et al
., 1984). This protein has been isolated
from the livers and several other tissues of Cd-exposed
animals.
The small size of the metallothionein molecule
enables the protein to be fi ltered through the kidney
glomerular membrane. Like other proteins in the
primary urine, metallothionein is reabsorbed into
proximal tubular cells. The transport of Cd bound to
metallothionein from the blood to renal tubular cells
is rapid and almost complete (Johnson and Foulkes,
1980; Nordberg and Nordberg, 1975). Cadmium not
bound to metallothionein does not enter the kidneys
to the same extent. A similar difference was observed
in animals fed cadmium-metallothionein and cad-
mium chloride (Cherian
et al
., 1978). The former gave
rise to a much higher accumulation of Cd in the renal
cortex than the latter, most probably because Cd from
the chloride binds to albumin (Nordberg, 1978).
Cadmium exposure induces the synthesis of metal-
lothionein in a number of tissues (Elinder and Nord-
berg, 1985). During the fi rst 12 hours after a high acute
exposure to Cd (not bound to metallothionein), there
will be an increase over time of Cd bound to metal-
lothionein as a result of the increased production of the
protein (Leber and Miya, 1976; Nordberg,
et al
., 1971a).
Because the transport of Cd to the kidney depends on
the metallothionein binding of Cd in plasma, the distri-
bution of Cd within the body after acute exposure will
be different from that after repeated exposures. Figure
2 presents a scheme, fi rst presented by G. Nordberg
(1984), describing the transport of Cd in the blood and
its uptake into kidney tubules. A detailed description
(Nordberg
et al
., 1985b) constituting the background
for this scheme was also presented by WHO/IPCS
(1992) and by Nordberg and Nordberg (2000). Imme-
diately after uptake of Cd from the gastrointestinal
tract or the lungs, the Cd is bound mainly to albumin
and other larger proteins in blood plasma. There is,
however, only limited information on the variation of
binding with time, dose, and route of administration in
animals, and none in humans. Available evidence indi-
cates that there is a pattern with proportionally more
plasma Cd in a low-molecular-weight form (probably
mainly bound to metallothionein [MT]) when low
doses of Cd are given through the oral route compared
with that when large doses are given through injection.
There is also a time dependence of plasma binding,
with a larger proportion of plasma-Cd being bound to
low-molecular-weight plasma proteins at longer time
intervals after a single administration.
Cadmium bound to albumin is to a large extent taken
up by the liver, where the complex is split, and Cd can
cause toxicity to liver cells (at relatively high doses,
particularly after injection). Cadmium also induces the
Renal tubular cell
Liver cell
Tubular fluid
Bile
Plasma
GSH
Sensitive
site
Cd-GSH
Cd-GSH
aa
MT
−
−
Cd-Alb
?
Cd-Alb
?
Cd
Damage
aa
Lysosome
Cd-MT
Cd-MT
Cd-MT
Cd-MT
Cd
MT
aa
aa
To urine
Cd-MT
Glomerular
membrane
FIGURE 2
Basic fl ow scheme of cadmium in the body demonstrating the role of binding forms in blood and
metallothionein synthesis and degradation. GSH: glutathione; MT: metallothionein; aa: amino acids; Alb:albumin
(Modifi ed from Nordberg, G., 1984).
