Chemistry Reference
In-Depth Information
Sarosiek
et al
., 1989; Vakil and Cutler, 1999). Vondracek
(1998) concluded that the antimicrobial and mucosal
protective effects of bismuth contributed to the eradi-
cation of the
H. pylori
infection. In an assessment of the
treatments of more than 50,000 patients throughout
the world with
H. pylori
, Laheij
et al
. (1999) estimated
effectiveness in approximately 80-85% of patients.
Treatments were usually combinations of ranitidine bis-
muth citrate or proton-pump inhibitor (PPI) with two
antibiotics. Sometimes treatments were a combination
of a PPI or H2 receptor antagonist with bismuth subci-
trate or tripotassium dicitrato bismuthate, metronida-
zole, and tetracycline. Because of expense, PPI-based
treatments are less often used in developing countries
(de Boer, 1999). The choice of the bismuth compound
does not seem to be an important factor (Megraud,
2000).
On the basis of an analysis of fi ve randomized clini-
cal trials related to treatment of collagenous colitis,
Chande and coauthors (2004) concluded that patients
improved clinically and histologically but were not
convinced that there was remission of the disease.
Bismuth has also been found to be useful for assist-
ance in wound healing (Mai
et al
., 2003). Bismuth sub-
gallate has been commonly used as an astringent and
hemostatic in adenotonsillectomies in the form of bis-
muth subgallate-epinephrine paste. Conley and Elli-
son (1999) conducted a case series study that showed
a reduction in posttonsillectomy hemorrhage when
bismuth subgallate was applied to the surgical site.
However, on the basis of a review of the literature, Hat-
ton (2000) concluded that it was probably the epine-
phrine that was the hemostatic agent. Tramontina
et al
. (2002), though, did fi nd that bismuth subgallate
promoted wound healing in rats. Bismuth induction
of metallothionein has been shown to reduce the car-
diotoxicity of Adriamycin in mice (Satoh
et al
., 2000)
and renal toxicity of cis-diammine dichloro-platinum
(Kondo
et al
., 1993) in cancer patients and in mice
(Kondo
et al
., 2004) treated with bismuth subnitrate.
The tagging of antibodies to surface proteins on leuke-
mia cells with the alpha-particle emitting 212Bi or 213Bi
isotopes has shown promise in helping to kill these
malignant cells (Kennel
et al
., 1999; Kolbert
et al
., 2001;
Macklis
et al
., 1992; Vandenbulcke
et al
., 2003) appar-
ently by a mechanism involving induction of apopto-
sis (Macklis
et al
., 1992; Vandenbulcke
et al
., 2003). This
approach has also be used to study the
in vitro
toxicity
of
11 3
Bi-labeled plasminogen activator inhibitor type 2
to human breast cancer cells (Ranson
et al
., 2002).
Shields incorporating bismuth have been used as
protection against radiation during diagnostic imag-
ing procedures, such as computed tomography, and
shown to reduce radiation exposure to sensitive organ
systems (Colombo
et al
., 2004; Fricke
et al
., 2003; Hopper
et al
., 1997; King
et al
., 2002).
7.2 Systemic Effects and Dose-Response
Relationships
The main systemic effects of bismuth compounds
both in man and in animals are exerted in the liver and
kidney.
7.2.1 Animals
7.2.1.1 Liver
Cloudy swelling with nuclear degeneration and occa-
sional small foci of necrosis in the liver were observed in
rabbits after lethal injections of sodium and potassium
tartro-bismuthate (intravenous, 10-30
g/kg; intramus-
cular, 150-350 mg/kg) and bismuth trioxide (intramus-
cular, 450 and 500
µ
g/kg) (Lucke and Klander, 1923).
After 6 months, peroral treatment of rats and rabbits
with potassium bismuthate (2.5, 0.25, 0.025, and 0.05
µ
µ
g/
kg) and bismuth sulfate (5.0, 0.5, 0.05, and 0.025
g/kg)
produced dilatation of intertrabecular capillaries, vas-
cular stasis, and marked dilatation and congestion of
the vessels. The hepatic tissue contained large irregu-
larly shaped foci of reticuloendothelial cells. The sever-
ity of these changes was closely related. The activity of
succinic dehydrogenase in the liver and of cholineste-
rase in the serum and liver was reduced even at doses
of 0.025 and 0.05
µ
g/kg. Hepatic excretory function was
abnormal in rabbits (bromsulfthalein retention). There
were no effects when animals were given 0.0005
µ
µ
g/kg
potassium bismuthate and 0.025
g/kg bismuth sulfate
(Seljankina
et al
., 1970). Woods and Fowler (1987) stud-
ied liver toxicity in rats after subcutaneous injections of
bismuth subnitrate at doses of 0, 20, 40, and 80
µ
g/kg
16 hours after injection by electron microscopy. They
reported swollen mitochondrial membranes in liver
cells of rats given the bismuth injections that was most
marked in animals receiving the two highest dose lev-
els. The morphological changes were correlated with
dose-related decreases in the mitochondrial heme path-
way enzymes ALA-synthetase and heme synthetase
(ferrochelatase), as well as the cytosolic enzyme ALA-
dehy dratase.
µ
7.2.1.2 Kidney
Kidney damage was produced in rats by single
intramuscular injections (0.03-1.5 g/kg) of 13 different
bismuth compounds. Histological examination of 104
rats showed that 36 or 37 animals that died before 21
days had nephritis of varying degrees of severity as
had 11 of the 67 surviving rats. The proximal tubules
constituted the most markedly affected site of toxicity.
