Cadmium - Toxicology of Metals - page 453

demonstrated in experiments performed on STZ dia-
betic rats during short time intervals (Jin et al ., 1996).
Increased binding of Cd to MT occurred in the liver of
the STZ-injected animals 24 hours after the injection of
CdMT and parallel to an increased resistance to neph-
rotoxicity. Induction of MT by STZ thus protects against
nephrotoxicity. In long-term experiments of the effects
of Cd in drinking water (Bernard et al ., 1991; Jin et al .,
1999), the response of rats having STZ-induced diabe-
tes was compared with that of similar animals without
diabetes. Compared with nondiabetic animals, animals
with diabetes developed more prominent nephropa-
thy. Another diabetes model is the use of Umeå obob
obese mice, which are similar metabolically to type II
diabetic humans. It was demonstrated (Jin et al ., 1994)
that there is an increased susceptibility to the develop-
ment of Cd-MT-induced proteinuria and calciuria in
the Umeå obob mice relative to that of normal mice
(Jin et al ., 1994).
Cadmium workers exhibiting increased plasma levels
of antibodies against MT developed renal tubular dys-
function at lower levels of urinary Cd than did workers
without such increased plasma levels (cf. Section 7.5.1.
and Chen et al ., 2006b). Cadmium exposure is of concern
for subjects with thalassemia, because it cannot be ruled
out that such persons may be particularly sensitive to
the adverse effects of Cd exposure (cf. Section 7.2.4).

Mediterranean (i.e., in populations originating from
Cyprus, Egypt, Greece, Italy, Lebanon, Malta, Turkey,
and the Middle East) as well as in India and some parts
of South East Asia, including Thailand, China, and the
Philippines. In areas with intake of foodstuffs that con-
tain Cd, these populations will probably be at increased
risk of toxicity from Cd because of the increased risk
of hemolysis. No studies, however, have examined the
potentially increased Cd susceptibility of persons with
these genetically inherited disorders.

7.2.5 Blood Pressure

Since the fi rst report describing that the administra-
tion of Cd elevated the blood pressure of rats (Schroeder
and Vinton, 1962), numerous animal experiments
have been conducted that variously support or dis-
pute this observation. Although mechanisms devised
to explain the elevation of blood pressure suggest the
involvement of the renin-angiotensin system (Perry
and Erlanger, 1973), monoamine oxidase (Revis, 1978),
catechol-O-methyltransferase (Revis, 1978), endothe-
lin (Ozdem and Ogutman, 1997; Wada et al ., 1991), and
nitric oxide (Demontis et al ., 1998), no consensus has
yet been reached.
With respect to the relationship between Cd and
blood pressure in humans, whereas some reports have
described that renal Cd concentrations and Cd/Zn
ratios were elevated in hypertensive autopsied cases
(Schroeder, 1965) and that blood Cd concentrations of
hypertensive subjects exceeded those of normotensive
subjects (Glauser et al ., 1976; Luoma et al ., 1995), others
have reported no differences between the two groups
(Beevers et al ., 1976; Fontana and Boulos, 1986; Staessen
et al ., 1991). No reports have noted the development of
hypertension in Cd workers. In a survey of inhabitants
of a Cd-polluted region in Japan, a tendency for low
blood pressure was found in 471 women with renal
injury compared with 2308 women in a control area
(Nogawa and Kawano, 1969). Furthermore, hyperten-
sion has not been observed in Itai-Itai disease patients
or in persons requiring observation for such disease
(Kagamimori et al ., 1986; Shinoda et al ., 1977). These
authors noted low systolic and diastolic pressures
among Itai-Itai disease patients. The Cd concentra-
tions in the blood (Basun et al ., 1994) of an aged popu-
lation was found to be related to the diastolic blood
pressure in nonsmoking and nondemented individu-
als. The observed differences in the Cd concentrations
in blood were related to smoking habits (Basun et al .,
1994); thus, the relationship to blood pressure may be
explained by considering the effects of smoking. In a
follow-up study (Nordberg et al ., 2000) of 804 subjects,
both men and women, aged 77 years and older, with a
mean age of 87 years, blood-Cd was analyzed among

7.2.4 Anemia

Slightly decreased hemoglobin concentrations were
observed in Cd workers but were found to be revers-
ible changes unrelated to renal injury (Friberg, 1950;
Toda et al ., 1984). However, in Itai-Itai disease patients
who have the most severe form of Cd poisoning, extr-
emely severe anemia with red blood cell counts of
1,155,000/mm 3 and hemoglobin of 4.2 g/dL (42 g/L)—
is found. In a group of 10 Itai-Itai disease patients in
whom serum iron, ferritin, and erythropoietin levels
and renal function were determined, as well as bone
marrow aspiration performed, the anemia was noted
to be normochromic, with no decreases in the iron or
serum ferritin levels and no particular abnormalities
noted from smears of bone marrow aspirates. On the
other hand, serum erythropoietin concentrations were
markedly decreased, the cause of which was ascribed
to renal anemia (Horiguchi et al ., 1994). In patients
with Itai-Itai disease, normal liver Fe concentrations
are found (Nogawa et al ., 1984). In animal experiments,
the administration of Cd has been reported to result in
the development of iron-defi ciency anemia and renal
anemia (Hiratsuka et al ., 1996).
Subjects with thalassemia and hematochromatosis
exhibit disturbed patterns of their hemoglobin. Car-
riers of the thalassemia gene are found around the