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Table of Contents | |
- BISMUTH
-
- Title
Increased biliary excretion of glutathione is generated by the
glutathione-dependent hepatobiliary transport of antimony and bismuth.
Author
Gyurasics A; Koszor´us L; Varga F; Gregus Z
Address
Department of Pharmacology, University Medical School of P´ecs, Hungary.
Source
Biochem Pharmacol, 44(7):1275-81 1992 Oct 6
Abstract
We have recently demonstrated that the hepatobiliary transport of arsenic is
glutathione-dependent and is associated with a profound increase in biliary
excretion of glutathione (GSH), hepatic GSH depletion and diminished GSH
conjugation (Gyurasics A, Varga F and Gregus Z, Biochem Pharmacol 41: 937-944
and Gyurasics A, Varga F and Gregus Z, Biochem Pharmacol 42: 465-468, 1991).
The present studies in rats aimed to determine whether antimony and bismuth,
other metalloids in group Va of the periodic table, also possess similar
properties. Antimony potassium tartrate (25-100 mumol/kg, i.v.) and bismuth
ammonium citrate (50-200 mumol/kg, i.v.) increased up to 50- and 4-fold,
respectively, the biliary excretion of non-protein thiols (NPSH). This
resulted mainly from increased hepatobiliary transport of GSH as suggested by
a close parallelism in the biliary excretion of NPSH and GSH after antimony or
bismuth administration. Within 2 hr, rats excreted into bile 55
and 3% of the dose of antimony (50 mumol/kg, i.v.) and bismuth
(150 mumol/kg, i.v.), respectively. The time courses of the biliary excretion
of these metalloids and NPSH or GSH were strikingly similar suggesting
co-ordinate hepatobiliary transport of the metalloids and GSH. However, at the
peak of their excretion, each molecule of antimony or bismuth
resulted in a co-transport of approximately three molecules of GSH. Diethyl
maleate, indocyanine green and sulfobromophthalein (BSP), which decreased
biliary excretion of GSH, significantly diminished excretion of antimony and bismuth
into bile indicating that hepatobiliary transport of these metalloids is GSH-dependent.
Administration of antimony, but not bismuth, decreased hepatic
GSH level by 30% and reduced the GSH conjugation and biliary excretion of BSP.
These studies demonstrate that the hepatobiliary transport of trivalent
antimony and bismuth is GSH-dependent similarly to the
hepatobiliary transport of trivalent arsenic. Proportionally to their biliary
excretion rates, these metalloids generate increased biliary excretion of GSH
probably because they are transported from liver to bile as unstable GSH
complexes. The significant loss of hepatic GSH into bile as induced by arsenic
or antimony may compromise conjugation of xenobiotics with GSH.
- Title
Pharmacokinetics and toxicity of bismuth compounds.
Author
Slikkerveer A; de Wolff FA
Address
Toxicology Laboratory, University Hospital, Leiden, The Netherlands.
Source
Med Toxicol Adverse Drug Exp, 4(5):303-23 1989 Sep-Oct
Abstract
Inorganic bismuth salts are poorly soluble in water:
solubility is influenced by the acidity of the medium and the presence of
certain compounds with (hydr)oxy or sulfhydryl groups. The analysis of bismuth
in biological material is not standardised and is subject to large variation;
it is difficult to compare data from different studies, and older data should
be approached with caution. The normal concentration of bismuth
in blood is between 1 and 15 micrograms/L, but absorption from oral
preparations produces a significant rise. Distribution of bismuth
in the organs is largely independent of the compound administered or the route
of administration: the concentration in kidney is always highest and the
substance is also retained there for a long time. It is bound to a bismuth-metal
binding protein in the kidney, the synthesis of which can be induced by the
metal itself. Elimination from the body takes place by the urinary and faecal
routes, but the exact proportion contributed by each route is still unknown.
Elimination from blood displays multicompartment pharmacokinetics, the
shortest half-life described in humans being 3.5 minutes, and the longest 17
to 22 years. A number of toxic effects have been attributed to bismuth
compounds in humans: nephropathy, encephalopathy, osteoarthropathy,
gingivitis, stomatitis and colitis. Whether hepatitis is a side effect,
however, is open to dispute. Each of these adverse effects is associated with
certain bismuth compounds. Bismuth encephalopathy
occurred in France as an epidemic of toxicity and was associated with the
intake of inorganic salts including bismuth subnitrate,
subcarbonate and subgallate. In the prodromal phase patients developed
problems in walking, standing or writing, deterioration of memory, changes in
behaviour, insomnia and muscle cramps, together with several psychiatric
symptoms. The manifest phase started abruptly and was characterised by changes
in awareness, myoclonia, astasia and/or abasia and dysarthria. Patients
recovered spontaneously after discontinuation of bismuth.
Intestinal lavage, forced diuresis and haemodialysis have been tried without
positive effects on the clinical condition of the patient or on blood bismuth
concentration, and the use of dimercaprol as an antidote has produced reports
of both positive and negative findings. To confirm the diagnosis of bismuth
encephalopathy, it is essential to find elevated bismuth
concentrations in blood, plasma, serum or CSF. A safety level of 50
micrograms/L and an alarm level of 100 micrograms/L have been suggested in the
past, but no proof is available to support the choice of these
levels.(ABSTRACT TRUNCATED AT 400 WORDS)
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