Chemistry Reference
In-Depth Information
of Leyding cells in relation to testicular macrophages.
This investigator found no effect on the secretion of
tumor necrosis factor (TNF-alpha) and concluded that
bismuth does not directly affect Leydig cells but rather
decreases serum testosterone concentrations by means
of toxicity to testicular macrophages. Arata
et al
. (2002)
studied the cytotoxic effects of triphenylbismuth rela-
tive to bismuth chloride and triphenyl tin chloride in
rat thymocytes. They found that triphenyl bismuth at
a concentration of 30
muth sodium triglycollate or thioglycollate, particu-
larly in children (Boyette, 1946; Urizar and Vernier,
1966). The tubular epithelium is mainly affected with
little change in the glomeruli. In 30 cases of bismuth
nephropathy reviewed by Urizar and Vernier, the
interval between medication and onset of symptoms
and signs ranged from 6-7 weeks (mainly bismuth
sodium thioglycollate, intramuscular doses 5-200
g;
oral, 1.5-19 g). Functional alterations in acute bismuth
nephropathy include severe depression of glomerular
fi ltration rate, renal plasma fl ow, and proximal tubular
reabsorption, as indicated by glucosuria, phosphatu-
ria, and aminoaciduria (Czerwinski and Ginn, 1964).
Bismuth inclusions were found in the renal tubular
epithelium of 12 of the 14 patients treated parenterally
with bismuth compounds (Beaver and Burr, 1963b).
µ
mol/L increased the number of
thymocytes positive for annexin V binding, suggesting
an increase in apoptosis. At a 3
µ
mol/L concentration,
they observed both a decrease in cellular glutathione
and an increase in intracellular Ca2
+
. Bismuth chloride
did not signifi cantly alter cellular viability over a 10-
30
µ
µ
mol/L concentration range.
7.2.2.3 Neurological Effects
A neurological syndrome possibly associated with
bismuth subgallate ingestion and characterized by
confusion, tremulousness, clumsiness, myoclonic jerks,
and gait disturbance was observed in four patients
(Burns
et al
., 1974). Robertson (1974) also described
similar neuropsychiatric symptoms and signs in four
geriatric patients administered large doses of the
same compound orally for several months. Emile
et al
.
(1981) reported 59 cases of bismuth encephalopathy
between 1972 and 1979 with serum bismuth concen-
trations between 900 and 2320
7.2.2 Humans
Although bismuth compounds had been used for
the treatment of syphilis and for other therapeutic
uses, Beerman (1932) compiled only 22 fatalities result-
ing from such therapy. Delayed deaths were mainly
attributable to the involvement of the gastrointestinal
tract, the liver, or the kidney, or a combination of the
two or all three of these systems. Deaths of 11 children
occurred within 2-5 days after the use of suppositories
containing bismuth salt of heptadiencarboxylic acid and
were preceded by vomiting, drowsiness, abdominal
pain, convulsions, and coma (Weinstein, 1947). There
are no reports on the occupational exposure effects of
bismuth (Filipova, 1971). No effects were observed in
13 normal volunteers receiving approximately 450
g/L. More recent stud-
ies using silver enhanced staining of brain sections
from six patients with bismuth toxicity showed that
bismuth accumulated in both neurons and glial cells
in various brain regions (Stoltenberg
et al
., 2001). The
blood vessels of the cerebellum also showed intense
staining. Tissue analyses using proton-induced X-ray
emission analysis and atomic absorption spectroscopy
confi rmed the presence of bismuth in affected brain
regions. By electron microscopy, bismuth was found
in the lysosomes and along the vasculature basement
membranes. Follow-up studies in rats using bismuth
subnitrate injections (Stoltenberg
et al
., 2003) showed
reduction in the numbers of A and B cells in the nerve
roots but not the area of axonal cross-sections or myeli-
nated nerve fi bers in the ventral or dorsal root of the
dorsal root ganglion. These types of neuronal effects
are consistent with the observations of myoclonic
encephalopathy reported in persons with chronic bis-
muth abuse (Teepker
et al
., 2002).
µ
g
Bi daily (as “Bistrimate” [bismuth sodium triglycol-
lamate]-C
24
H
28
O
25
N
4
BiNa
7
) from a few days to over
a year (Lehman and Fassett, 1947).
µ
7.2.2.1 Liver
An instance of jaundice with liver damage was
reported in a 6-year-old child who received 4-5
g/kg
body weight of bismuth thioglycollate in a single injec-
tion. On the basis of this and a number of fatal cases
reported by other authors, Karelitz and Freedman
(1951) concluded that soluble bismuth compounds are
defi nitely hepatotoxic to man, producing fatty degen-
eration of the liver. This confi rms the analysis of Beer-
man (1932) and Wolman (1940). Jaundice indicative of
hepatitis occurred in 10.3% of 1032 syphilis patients
treated with bismuth compounds between 1932 and
1942 (Kulcher and Reynolds, 1942).
µ
7.2.2.4 Skin and Mucosa
Pityriasis, rosea-like eruptions, and other skin
manifestations such as the “erythema of the ninth
day” syndrome (Milian's erythema) have been occa-
sionally described as a result of therapy with bismuth
7.2.2.2 Kidney
Acute renal failure can occur after oral or parenteral
administration of bismuth compounds such as bis-
