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Mercury

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Title
Factors affecting internal mercury burdens among eastern German
children.
Author
Trepka MJ; Heinrich J; Krause C; Schulz C; Wjst M; Popescu M; Wichmann
HE
Address
GSF-Forschungszentrum für Umwelt und Gesundheit, Institut für
Epidemiologie, Oberscheissheim, Germany.
Source
Arch Environ Health, 52(2):134-8 1997 Mar-Apr
Abstract
Internal burdens of mercury were evaluated among 5- to 14-y-old eastern
German children in the heavily polluted areas of Bitterfeld, a center
of chemical production and coal mining, and Hettstedt, a region of
nonferrous metal smelting and mining. We compared blood and urine
mercury concentrations in these children with mercury burdens in
children who lived in a control area. The unadjusted geometric means of
mercury levels in the total group were 0.25 microg/l (95% confidence
interval = 0.24, 0.27) in blood and 0.36 microg mercury/g creatinine
(95% confidence interval = 0.33, 0.39) in urine. mercury levels in
blood and urine were not significantly higher in children who occupied
the two polluted areas, compared with children in the control area. The
most significant factor that affected urinary mercury levels was the
number of dental amalgam fillings; 27% of the variance in the
regression model was explained by the presence of these fillings.

Title
Antimicrobial and mercury resistance in aerobic gram-negative bacilli
in fecal flora among persons with and without dental amalgam fillings.
Author
Osterblad M; Leistevuo J; Leistevuo T; Järvinen H; Pyy L; Tenovuo J;
Huovinen P
Address
Antimicrobial Research Laboratory, National Public Health Institute,
Turku, Finland.
Source
Antimicrob Agents Chemother, 39(11):2499-502 1995 Nov
Abstract
Antimicrobial resistance is more widespread than can be accounted for
as being a consequence of the selection pressure caused by the use of
antibiotics alone. In this study, we tested the hypothesis that a high
mercury content in feces might select for mercury-resistant bacteria
and thus for antimicrobial resistance linked to mercury resistance.
Three subject groups with different exposures to dental amalgam
fillings were compared. None of the subjects had taken antimicrobial
agents during the three preceding months or longer. The group exposed
to dental amalgam (n = 92) had 13 times more mercury in feces than the
group that had never been exposed to amalgam (n = 43) and the group
whose amalgam fillings had been removed (n = 56). No significant
differences in either mercury resistance or antibiotic resistance in
the fecal aerobic gram-negative flora of these subject groups were
seen. The following antimicrobial resistance frequencies were detected
with a replica plating method: > or = 1% resistance was seen in 40% of
the subjects for ampicillin, 14% of the subjects for cefuroxime, 6% of
the subjects for nalidixic acid, 14% of the subjects for trimethoprim,
19% of the subjects for sulfamethoxazole, and 25% of the subjects for
tetracycline. The amount of mercury in feces derived from amalgam was
not selective for any resistance factors in aerobic gram-negative
bacteria, but antimicrobial resistance was widespread even among
healthy subjects with no recent exposure to antibiotics.

Title
Effect of different renal glutathione levels on renal mercury
disposition and excretion in the rat.
Author
Girardi G; Elías MM
Address
Facultad de Ciencias, Bioquímicas y Farmacéuticas, Universidad Nacional
de Rosario, República Argentina.
Source
Toxicology, 81(1):57-67 1993 Jul 11
Abstract
mercury renal disposition has been studied following HgCl2 injection
(5.0 mg/kg body wt., s.c.) in controls, diethylmaleate and
N-acetylcysteine-treated rats. The different treatments were used to
generate statistically different degrees of non-protein sulfhydryls
concentration in kidneys. Diethylmaleate (4 mmol/kg body wt., i.p.)
diminished kidney glutathione levels to 25% and N-acetylcysteine (2
mmol/kg body wt., i.p.) increased kidney non-protein sulfhydryls levels
up to 75% compared with new controls. The amount of mercury in the
kidneys, the mercury excretion rate in urine and the mercury plasma
disappearance curves were calculated during 3 h post HgCl2 injection.
BUN was measured in plasma at the same time period to determine the
onset of kidney damage. The results indicate a higher HgCl2 renal
clearance in N-acetylcysteine-treated rats compared to controls and
less renal mercury accumulation. The data agree with diminished renal
toxicity. On the other hand, renal mercury accumulation was higher and
mercury renal clearance lower in diethylmaleate-treated animals,
associated with higher renal toxicity. The results suggest that
non-protein sulfhydryl levels (principally glutathione) might determine
renal accumulation of mercury as well as its elimination rate and hence
might enhance or mitigate the nephrotoxicity induced by the metal.

Title
Mechanisms of metal transport across liver cell plasma membranes.
Author
Ballatori N
Address
Department of Biophysics, University of Rochester School of Medicine,
New York 14642.
Source
Drug Metab Rev, 23(1-2):83-132 1991
Abstract
The liver's pivotal role in the homeostasis of essential trace metals
and detoxification of exogenous metals is attributed to its ability to
efficiently extract metals from plasma, metabolize, store, and
redistribute them in various forms either into bile or back into the
bloodstream. Bidirectional transport across the sinusoidal plasma
membrane allows the liver to control plasma concentrations and
therefore availability to other tissues. In contrast, transport across
the canalicular membrane is largely, but not exclusively,
unidirectional and is a major excretory pathway. Although each metal
has relatively distinct hepatic transport characteristics, some
generalizations can be made. First, movement of metals from plasma to
bile follows primarily a transcellular route. The roles of the
paracellular pathway and of ductular secretion appear minimal. Second,
intracellular binding proteins and in particular metallothionein play
only indirect roles in transmembrane flux. The amounts of
metallothionein normally secreted into plasma and bile are quite small
and cannot account for total metal efflux. Third, metals traverse liver
cell plasma membranes largely by facilitated diffusion, and by
fluid-phase, adsorptive, and receptor-mediated endocytosis/exocytosis.
There is currently no evidence for primary active transport. Because of
the high rate of hepatocellular membrane turnover, metal transport via
endocytic vesicles probably makes a larger contribution than previously
recognized. Finally, there is significant overlap in substrate
specificity on the putative membrane carriers for the essential trace
metals. For example, zinc and copper share many transport
characteristics and apparently compete for at least one common
transport pathway. Similarly, canalicular transport of five of the
metals discussed in this overview (Cu, Zn, Cd, Hg, and Pb) is linked to
biliary GSH excretion. These metals may be transported as GSH complexes
by the canalicular glutathione transport system(s). Unfortunately, none
of the putative membrane carrier proteins have been studied at the
subcellular or molecular level. Our knowledge of their biochemical
properties is rudimentary and rests almost entirely on indirect
evidence obtained in vivo or in intact cell systems. The challenge for
the future is to isolate and characterize these putative metal
carriers, and to determine how they are functionally regulated.

Title
Biliary secretion of glutathione and of glutathione-metal complexes.
Author
Ballatori N; Clarkson TW
Source
Fundam Appl Toxicol, 5(5):816-31 1985 Oct
Abstract
As bile is the main route of elimination of many metals, a large number
of studies have been directed toward the characterization of the
hepatobiliary transport of both endogenous and exogenous metals.
Although some progress has been made, we still know little of the basic
mechanisms involved in the hepatocellular uptake of metals, in their
intracellular translocation and metabolism, or in their transport into
bile. Our recent studies have focused on the last step in the
hepatobiliary transport of mercury, namely, the secretion of the metal
from liver cells into bile. The rate of secretion of methyl and
inorganic mercury into bile was low in suckling rats and rapidly
increased to adult rates soon after weaning. These changes closely
followed similar developmental changes in the biliary secretion of
reduced glutathione (GSH). When GSH secretion into bile was completely
inhibited, without changing hepatic levels of GSH or mercury, mercury
secretion was also completely blocked. mercury secretion paralleled
individual and sex-related differences in GSH secretion. At the same
time, the secretion of mercury was independent of bile flow, of the
thiol and mercury concentration gradients between bile and liver cells,
and of those between bile and plasma. Our results, therefore, indicate
a close coupling between the secretion of mercury and that of GSH.
These in vivo findings, along with in vitro studies by others in
vesicles isolated from the canalicular membrane of the liver cell,
indicate a carrier-mediated transport system for GSH, but the nature of
the linkage of this transport system with mercury secretion is not yet
fully established. Our data and those in the literature are consistent
with the involvement of at least two steps in the movement of mercury
from liver cells to bile--the formation of a mercury-glutathione
complex in the liver cell, followed by the secretion of this complex
through a process closely linked to GSH secretion. The identification
of GSH as an endogenous complexing agent in the transport of metals
between tissues and body fluids now permits the design of therapeutic
strategies aimed at exploiting this transport vehicle to effect the
removal of metals via physiological routes of excretion. The present
discussion considers the role of GSH in the hepatobiliary transport of
metals. In doing so, a brief review is given of current understanding
of hepatic GSH metabolism and transport.

Title
Mechanisms of hepatic methylmercury uptake.
Author
Ballatori N; Truong AT
Address
Department of Environmental Medicine, University of Rochester School of
Medicine, NY 14642, USA.
Source
J Toxicol Environ Health, 46(3):343-53 1995 Nov
Abstract
The mechanism by which methylmercury is cleared from hepatic portal
blood was examined in isolated rat livers perfused single-pass with
Krebs-Henseleit buffer. [203Hg]Methylmercury (0.24-24 microM) was
infused over a 30-min interval, followed by a 30-min washout, as a
complex with the endogenous ligands L-cysteine (CH3Hg-L-cys),
glutathione (CH3Hg-SG), and serum albumin (CH3Hg-albumin), or as a
complex with dithiothreitol (CH3Hg-DTT), chloride (CH3HgCl), and the
D-enantiomer of cysteine (CH3Hg-D-cys). The sulfhydryl-containing
compounds were added at a 10-fold molar excess. When administered as
the albumin complex, only a small fraction of the [203Hg]methylmercury
was cleared from perfusate (approximately 8%) and excreted into bile
(0.7%). Hepatic uptake and biliary excretion of methylmercury was
considerably higher for the other complexes: The percent of the dose
recovered in liver tissue and bile was, respectively, CH3Hg-albumin,
6.9 and 0.7; CH3Hg-L-cys, 15.7 and 2.3; CH3Hg-D-cys, 27.1 and 2.8;
CH3Hg-SG, 17.7 and 2.1; CH3HgCl, 66.5 and 3.2; and CH3Hg-DTT, 70.1 and
19.8. For the dithiothreitol complex, hepatic extraction of
methylmercury was nearly complete during single-pass perfusion. A
comparison of hepatic removal of increasing doses of CH3Hg-L-cys and
CH3Hg-D-cys revealed little difference in uptake between these two
enantiomers. Moreover, the fraction of methylmercury removed was
similar when infused at concentrations of 0.24, 2.4, and 24 microM,
indicating no saturability of uptake within this dose range.
Methylmercury was not hepatotoxic at concentrations up to 24 microM if
administered as a mercaptide; however, the chloride complex (CH3HgCl)
produced cholestasis and an increase in perfusion pressure at a
concentration of only 0.24 microM. These findings indicate that hepatic
methylmercury uptake and toxicity are dependent on the chemical form in
blood plasma. Uptake was faster when methylmercury was present as a
cysteine or glutathione complex, as compared to the albumin complex;
however, the lack of stereoselectivity indicates that the uptake
process may be relatively unselective.

Title
Nephrotoxicity of inorganic mercury co-administrated with L-cysteine.
Author
Zalups RK; Barfuss DW
Address
Division of Basic Medical Sciences, Mercer University of Medicine,
Macon, Georgia 31207, USA.
Source
Toxicology, 109(1):15-29 1996 May 3
Abstract
In the present study, we tested the hypothesis that co-administration
of low nephrotoxic doses of inorganic mercury (Hg++) with L-cysteine
(in a 1:2 mol ratio of inorganic mercury to L-cysteine), alters
significantly the nephropathy induced by inorganic mercury. In the
first experiment, the effect of co-administering L-cysteine on the
nephropathy induced by a 1.8 or 2.0 micromol/kg dose of inorganic
mercury was evaluated in rats 24 h after the administration of
inorganic mercury. According to histopathological assessment of
sections of kidney and evaluation of the urinary excretion of lactate
dehydrogenase, total protein and inorganic mercury (which were used as
indices of renal injury), the severity of renal injury in rats
co-administered the L-cysteine with the inorganic mercury was
significantly greater than that in corresponding rats injected with
only inorganic mercury. In a second experiment, the disposition of
mercury was evaluated 1 h after the administration of 1.8 micromol
inorganic mercury/kg with or without 3.6 micromol L-cysteine/kg. The
renal accumulation of mercury, specifically in the cortex and outer
stripe of the outer medulla, was significantly greater the rats
co-administered the inorganic mercury and L-cysteine than in the rats
given only inorganic mercury. In addition, the content of mercury in
the blood and liver was significantly lower, and the fraction of
mercury in the blood present in the plasma was significantly greater,
in the rats co-administered inorganic mercury and L-cysteine than in
the rats given only inorganic mercury. On the basis of the findings
from this study, the nephropathy induced by low nephrotoxic doses of
inorganic mercury is made more severe when the inorganic mercury is
co-administered in a 1:2 mol ratio with L-cysteine. Moreover, it
appears that the enhanced severity in the nephropathy induced by the
co-administration of inorganic mercury and L-cysteine is linked to an
increase in the tubular uptake of mercury in the cortex and outer
stripe of the outer medulla.

Title
Impaired biliary excretion and whole body elimination of methylmercury
in rats with congenital defect in biliary glutathione excretion.
Author
Ballatori N; Gatmaitan Z; Truong AT
Address
Department of Environmental Medicine, University of Rochester School of
Medicine, NY 14642, USA.
Source
Hepatology, 22(5):1469-73 1995 Nov
Abstract
Biliary excretion of methylmercury, a major route of elimination of
this toxic compound, was less than 2% of control in Eisai
hyperbilirubinemic (EHBR) rats, a mutant Sprague-Dawley strain with a
defect in biliary excretion of a variety of organic anions, including
glutathione S-conjugates and reduced glutathione (GSH). Biliary GSH
excretion in EHBR rats was also < 2% of controls, confirming previous
findings. Impaired biliary methylmercury and GSH excretion was not
explained by decreased hepatic content of these compounds. Indeed,
hepatic methylmercury and GSH concentrations in EHBR rats were actually
double those of controls. To assess the significance of the impaired
biliary excretion in the whole body elimination of the toxicant, 203Hg
excretion was measured over a 17-day period after intraperitoneal
administration of either 0.5 or 5 mumol/kg of 203Hg-methylmercury
chloride. The results for the two doses were similar. Methylmercury was
eliminated by a first order process; however, the biological half-line
was significantly longer in the EHBR rats, 46 to 54 days versus 18 to
22 days. Fecal excretion was the main route of elimination in both
control and mutant animals. At necropsy (17 days), 16% to 25% of the
203Hg dose was recovered in the liver of the EHBR rats, whereas livers
of control animals contained less than 2%of the administered dose.
These findings demonstrate the biliary excretion of methylmercury is
markedly impaired in EHBR rats and is associated with a low biliary GSH
excretion, providing support for the hypothesis that methylmercury is
normally transported across the canalicular membrane by a GSH-dependent
mechanism, and presumably as a GSH mercaptide (CH3Hg-SG).(ABSTRACT
TRUNCATED AT 250 WORDS)

Title
Transport of the glutathione-methylmercury complex across liver
canalicular membranes on reduced glutathione carriers.
Author
Dutczak WJ; Ballatori N
Address
Department of Environmental Medicine, University of Rochester School of
Medicine, New York 14642.
Source
J Biol Chem, 269(13):9746-51 1994 Apr 1
Abstract
Methylmercury transport across liver canalicular membranes into bile, a
major route of excretion of this toxic compound, is dependent upon
intracellular GSH, and a glutathione-methylmercury complex (CH3Hg.SG)
has been detected in liver tissue and bile. To examine whether the
CH3Hg.SG complex is itself transported across the canalicular membrane
and to identify the transport system involved, studies were performed
in isolated rat liver canalicular plasma membrane vesicles. Uptake of
CH3(203)Hg.SG (10 microM) into an osmotically active space was
temperature-sensitive and unaffected by either ATP (5 mM) or an
inwardly directed Na+ gradient (100 mM); however, CH3Hg.SG uptake was
enhanced by a valinomycin-induced K+ diffusion potential
(inside-positive) indicating that its transport was electrogenic.
Transport of CH3Hg.SG exhibited saturation kinetics with both high
affinity (Km = 12 +/- 2 microM, Vmax = 0.23 +/- 0.02 nmol.mg-1.20 s-1)
and low affinity (Km = 1.47 +/- 0.22 mM, Vmax = 1.23 +/- 0.14
nmol.mg-1.20 s-1) components. Uptake of this complex was inhibited by
GSH, the GSH analog ophthalmic acid, S-methyl, S-ethyl, S-butyl,
S-hexyl, S-octyl, and S-dinitrophenyl glutathione, but not by GSSG,
bile acids, amino acids, and P-glycoprotein inhibitors. Furthermore,
GSH competitively inhibited (Ki = 83 microM) and trans-stimulated
CH3Hg.SG uptake into the canalicular vesicles. These studies provide
the first kinetic characterization of a transport system for
glutathione-mercaptides and indicate that CH3Hg.SG is not a substrate
for the ATP-dependent, canalicular GSSG or glutathione S-conjugate
carriers, but appears to be a substrate for canalicular carriers that
also transport GSH. Because efflux systems for GSH are found in all
mammalian cells, transport of glutathione-metal complexes by such
carriers may be a common mechanism for the removal of methylmercury and
possibly other metals from cells.

Title
Mobilization of heavy metals by newer, therapeutically useful chelating
agents.
Author
Aposhian HV; Maiorino RM; Gonzalez-Ramirez D; Zuniga-Charles M; Xu Z;
Hurlbut KM; Junco-Munoz P; Dart RC; Aposhian MM
Address
Department of Molecular and Cellular Biology, University of Arizona,
Tucson 85721, USA.
Source
Toxicology, 97(1-3):23-38 1995 Mar 31
Abstract
Four chelating agents that have been used most commonly for the
treatment of humans intoxicated with lead, mercury, arsenic or other
heavy metals and metalloids are reviewed as to their advantages,
disadvantages, metabolism and specificity. Of these, CaNa2EDTA and
dimercaprol (British anti-lewisite, BAL) are becoming outmoded and can
be expected to be replaced by meso-2,3-dimercaptosuccinic acid (DMSA,
succimer) for treatment of lead intoxication and by the sodium salt of
2,3-dimercapto-1-propanesulfonic acid (DMPS, Dimaval) for treating
lead, mercury or arsenic intoxication. Meso-2,3-DMSA and DMPS are
biotransformed differently in humans. More than 90% of the DMSA
excreted in the urine is found in the form of a mixed disulfide in
which each of the sulfur atoms of DMSA is in disulfide linkage with an
L-cysteine molecule. After DMPS administration, however, acyclic and
cyclic disulfides of DMPS are found in the urine. The Dimaval-mercury
challenge test holds great promise as a diagnostic test for mercury
exposure, especially for low level mercurialism. Urinary mercury after
Dimaval challenge may be a better biomarker of low level mercurialism
than unchallenged urinary mercury excretion.

Title
A laser Raman spectroscopic study on the interaction of alkylmercury
with thiol and sulfur-containing compounds.
Author
Yamamoto R; Sumino K; Nakamae K
Address
Department of Public Health, Kobe University School of Medicine, Japan.
Source
Arch Toxicol, 69(2):127-31 1994
Abstract
The interaction of the methylmercury cation with sulfur compounds in
aqueous solution at physiological pH was studied by laser Raman
spectroscopy. Metal binding is shown to occur preferentially at the
sulfhydryl group of sulfur compounds. Raman frequencies of S-Hg
stretching of the one-to-one methylmercury-sulfhydryl or
sulfur-containing complexes were observed at approximately 330 cm-1.
There was no frequency shift when ligands were exchanged. However, the
relative intensity (I S-Hg/I C-Hg) was different. The relative
intensities of MeHg-thioglycerol, MeHg-cysteine and
MeHg-2-mercaptobenzothiazole were 0.18, 0.43 and 0.62, respectively.
Methyl-mercury shifted from combination states of lager relative
intensity to ones of smaller relative intensity. These results may cast
light on the distribution and excretion mechanisms of methylmercury in
the human body.

Title
Role of extracellular glutathione and gamma-glutamyltranspeptidase in
the disposition and kidney toxicity of inorganic mercury in rats.
Author
de Ceaurriz J; Payan JP; Morel G; Brondeau MT
Address
Laboratoire de Chimie-Toxicologie de l'Environnement, FacultÍe de
Pharmacie, Chatenay-Malabry, France.
Source
J Appl Toxicol, 14(3):201-6 1994 May-Jun
Abstract
The role of extracellular glutathione (GSH) and membrane-bound
gamma-glutamyltranspeptidase (gamma-GT) as contributory factors in the
disposition and toxicity of inorganic mercury (HgCl2, 1 mg kg-1, i.p.)
was investigated in rats pretreated with acivicin (AT-125, 10 mg kg-1),
a gamma-GT inhibitor. A high degree of gamma-GT inhibition (75%) and of
protection (90%) against HgCl2-induced nephrotoxicity was obtained in
gamma-GT-inhibited rats 24 h post-treatment. Pretreatment with acivicin
affected the fractional distribution profile of 203 Hg, resulting in a
twofold decrease in the renal incorporation of mercury 4 h
post-treatment and a threefold increase in the 24-h urinary excretion
of mercury. Plasma radioactivity remained constant over 24 h in rats
dosed with 203Hg alone, whereas it decreased by 60% between 4 h and 24
h in gamma-GT-inhibited rats. In gamma-GT-inhibited rats treated with
HgCl2 the renal and plasma reduced glutathione (GSH) content increased
by 68% and 330% respectively, as compared to controls. The gamma-GT
inhibition affected the distribution profile of mercury within urinary
proteins, shifting the binding of mercury from the
high-molecular-weight fraction (3% against 80%) to the
low-molecular-weight fraction (72% against 10%). A significant but less
impressive shift of mercury from the high- to the low-molecular-weight
fraction also arose in the plasma. These results taken together support
the pivotal role of extracellular GSH and membrane-bound gamma-GT in
the renal incorporation, toxicity and excretion of inorganic mercury in
rats.

Title
Accumulation and handling of inorganic mercury in the kidney after
coadministration with glutathione.
Author
Zalups RK; Barfuss DW
Address
Division of Basic Medical Sciences, Mercer University School of
Medicine, Macon, Georgia 31207, USA.
Source
J Toxicol Environ Health, 44(4):385-99 1995 Apr
Abstract
The accumulation and handling of mercury in the blood, kidneys, and
liver were evaluated and compared in rats 5 min, 1 h, and 24 h after
the intravenous administration of either a 0.25 mumol/kg dose of
inorganic mercury or a 0.25 mumol/kg dose of inorganic mercury plus a
0.5 mumol/kg dose of glutathione (GSH) to determine the possible role
of extracellular GSH and complexes of GSH and inorganic mercury in the
renal uptake and transport of inorganic mercury. Significantly more of
the injected dose of inorganic mercury was present in the blood of the
rats injected with inorganic mercury alone than in the blood of the
rats injected simultaneously with both inorganic mercury and GSH at all
times evaluated after injection. Of the mercury remaining in the blood,
however, significantly more mercury was in plasma fraction of blood in
the rats injected with both inorganic mercury and GSH than in the
plasma fraction of blood in the rats injected with inorganic mercury
alone. The blood and plasma findings indicate that much of the mercury
injected with GSH was in some complex that allowed the mercury to be
cleared from the blood more readily and prevented the mercury from
entering readily into red blood cells. The renal concentration of
mercury was significantly greater in the rats injected with both
inorganic mercury and GSH than in the rats injected with inorganic
mercury alone at 5 min and 1 h, but not 24 h, after injection. This
increased renal accumulation of mercury during the initial hours after
injection was due mainly to enhanced uptake and/or retention of mercury
in the renal cortex. Urinary excretion of mercury, over 24 h, was also
slightly, but significantly, greater in the rats injected with both
inorganic mercury and GSH simultaneously. These data indicate that
coadministration of a nontoxic dose of inorganic mercury with a twofold
higher amount (in moles) of GSH increases significantly the clearance
of mercury from the blood and increases the renal cortical accumulation
of inorganic mercury during the initial 1 h after injection. Moreover,
the data in this study are consistent with the hypothesis that
extracellular GSH is an important ligand to which mercuric ions bind,
and that complexes of inorganic mercury and GSH in the blood and/or
ultrafiltrate probably play a role in the renal uptake of some of the
mercury in blood after exposure to mercuric compounds.

Title
Acute and chronic toxicity of aromatic amines studied in the isolated
perfused rat liver.
Author
Ambs S; Neumann HG
Address
Department of Toxicology, University of Würzburg, Germany.
Source
Toxicol Appl Pharmacol, 139(1):186-94 1996 Jul
Abstract
Isolated perfused livers from male Wistar rats were used to study acute
and chronic toxic effects of carcinogenic aromatic amines. We
investigated the hypothesis that aromatic amines can generate reactive
oxygen species as part of their metabolism. Concentrations of 200-400
microM of 2-acetylaminofluorene (AAF), N-hydroxy-AAF,
trans-4-acetylaminostilbene (AAS), N-hydroxy-AAS, and
N-hydroxy-2-acetylaminophenanthrene in the recirculating perfusate were
not toxic in a 2-hr exposure time as assessed by LDH efflux into the
perfusate, glutathione excretion into bile, and changes of the
beta-hydroxybutyrate/acetoacetate ratio in the perfusate.
N-Acetoxy-AAF, however, was severely toxic. Menadione served as a
positive control. It is concluded that exposures likely to occur in
carcinogenicity studies with these aromatic amines will not be acutely
toxic. In additional experiments the isolated perfused liver system was
used to demonstrate chronic effects generated by feeding the
carcinogenic dose of 0.02% AAF for up to 12 weeks. The following
alterations were observed in livers from AAF-fed animals. excretion of
glutathione into bile is drastically reduced after 5 or more weeks,
increasingly less glucose is released into the perfusate, and oxygen
consumption is constantly increased by 20% after 3 and more weeks of
AAF feeding. Whereas the total glutathione level increased with time in
homogenates of such livers, it decreased in the mitochondrial fraction.
The results are interpreted as adaptive responses to chronic toxic
effects of AAF which may be related to the promoting properties of this
carcinogen.

Title
Effects of exercise training on the distribution of metallic mercury in
mice.
Author
Shimojo N; Arai Y
Address
Institute of Community Medicine, University of Tsukuba, Ibaraki, Japan.
Source
Hum Exp Toxicol, 13(8):524-8 1994 Aug
Abstract
1. The purpose of this study was to correlate exercise induced changes
of antioxidant enzymes with the distribution of mercury after mercury
vapour exposure in mice. 2. Exercise training consisted of swimming (1
h/day for 5 days/week) for 9 weeks. After 9 weeks of training,
swim-trained mice showed significantly elevated levels of catalase
(CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSHpx) in
their red blood cells, CAT and GSHpx in their kidneys and SOD in the
liver. 3. Exercised mice (Ex) and non-exercised mice (N.Ex) were
exposed to mercury vapour (3.5 mg m-3) for 1 h. mercury concentrations
were assayed in the blood, brain, heart, lungs, liver and kidneys along
with the mercury content of the entire body. The whole body mercury
content showed no significant difference in any measurement
(immediately, 24 h and 48 h after mercury exposure) between the Ex and
N.Ex groups. mercury concentrations in the Ex group were significantly
higher than the N.Ex group in the heart, whole blood, red blood cells
and the brain at 24 and 48 h; and in the plasma and kidneys at 24 h. 4.
It was concluded that exercise training is a factor in distribution
changes of mercury after exposure to mercury vapour, though it is not a
factor in the total absorption and excretion of mercury.

 

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