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Significant mercury
deposits in internal organs following the removal of dental
amalgam, & development of pre-cancer on the gingiva
and the sides of the tongue and their represented organs as
a result of inadvertent exposure to strong curing light
(used to solidify synthetic dental filling material)
& effective treatment: a clinical case report,
along with organ representation areas for each
tooth.
Omura Y, Shimotsuura Y, Fukuoka A, Fukuoka H, Nomoto T.
Heart Disease Research Foundation, New York, NY, U.S.A.
Acupunct Electrother Res 1996 Apr-Jun;21(2):133-60
Because of the reduced effectiveness of antibiotics
against bacteria (e.g., Chlamydia trachomatis,
alpha-Streptococcus, Borrelia burgdorferi, etc.) and
viruses (e.g., Herpes Family Viruses) in the presence of
mercury, as well as the fact that the 1st author has found
that mercury exists in cancer and pre-cancer cell nuclei,
the presence of dental amalgam (which contains about 50%
mercury) in the human mouth is considered to be a potential
hazard for the individual's health. In order to solve this
problem, 3 amalgam fillings were removed from the teeth of
the subject of this case study. In order to fill the newly
created empty spaces in the teeth where the amalgams had
formerly existed, a synthetic dental-filling substance was
introduced and to solidify the synthetic substance, curing
light (wavelength range reportedly between 400-520 nm) was
radiated onto the substance in order to accelerate the
solidifying process by photo-polymerization. In spite of
considerable care not to inhale mercury vapor or swallow
minute particles of dental amalgam during the process of
removing it by drilling, mercury entered the body of the
subject. Precautions such as the use of a rubber dam and
strong air suction, as well as frequent water suctioning
and washing of the mouth were insufficient. Significant
deposits of mercury, previously non-existent, were found in
the lungs, kidneys, endocrine organs, liver, and heart with
abnormal low-voltage ECGs (similar to those recorded 1-3
weeks after i.v. injection of radioisotope Thallium-201 for
Cardiac SPECT) in all the limb leads and V1 (but almost
normal ECGs in the precordial leads V2-V6) the day after
the procedures were performed. Enhanced mercury evaporation
by increased temperature and microscopic amalgam particles
created by drilling may have contributed to mercury
entering the lungs and G.I. system and then the blood
circulation, creating abnormal deposits of mercury in the
organs named above. Such mercury contamination may then
contribute to intractable infections or pre-cancer.
However, these mercury deposits, which commonly occur in
such cases, were successfully eliminated by the oral intake
of 100 mg tablet of Chinese parsley (Cilantro) 4 times a
day (for average weight adults) with a number of
drug-uptake enhancement methods developed by the 1st
author, including different stimulation methods on the
accurate organ representation areas of the hands (which
have been mapped using the Bi-Digital O-Ring Test), without
injections of chelating agents. Ingestion of Chinese
parsley, accompanied by drug-uptake enhancement methods,
was initiated before the amalgam removal procedure and
continued for about 2 to 3 weeks afterwards, and ECGs
became almost normal. During the use of strong bluish
curing light to create a photo-polymerization reaction to
solidify the synthetic filling material, the adjacent
gingiva and the side of the tongue were inadvertently
exposed. This exposure to the strong bluish light was found
to produce pre-cancerous conditions in the gingiva, the
exposed areas of the tongue, as well as in the
corresponding organs represented on those areas of the
tongue, and abnormally increased enzyme levels in the
liver. These abnormalities were also successfully reversed
by the oral intake of a mixture of EPA with DHA and Chinese
parsley, augmented by one of the non-invasive drug-uptake
enhancement methods previously described by the 1st author,
repeated 4 times each day for 2 weeks.
Symptomatic treatment of
brain tumor patients with sodium selenite, oxygen, and
other supportive measures.
Pakdaman A. Klinik fur komplimentare Onkologie und
Immuntherapie im Gesundheitspark Beelitz,
Beelitz-Heilstatten, Germany.
Biol Trace Elem Res 1998 Apr-May;62(1-2):1-6
Patients (16 women and 16 men) with brain tumors
previously treated conservatively by surgery, radiation,
and/or chemotherapy with typical symptoms of increased
intracranial pressure were consecutively enrolled to test
the effects of pharmacological dosages of sodium selenite
(selenase) in conjunction with other supportive therapies
(biological response modifiers, detoxification,
chemotherapy, immunotherapy, oxygen therapy). The rationale
for the use of sodium selenite was that the whole-blood
selenium levels were subnormal in 70% of the patients on
admission. Patients also frequently presented abnormal
levels of other minerals, especially lowered sodium and
elevated potassium levels, which appears to be
characteristic of brain tumor patients. Sodium selenite was
administered by infusion at dosages of 1000 microg Se in
physiological saline/d for 4-8 wk. In 76% of the patients,
a definite, and in 24% a slight improvement of the general
condition and a decrease in symptoms, such as nausea,
emesis, headache, vertigo, unsteady gait, speech disorders,
and Jacksonian seizures, were observed. In all treated
patients, improvements of erythrocyte, hemoglobin, and
thrombocyte counts were observed. Additional beneficial
effects were noted in the patients receiving the oxygen
therapy. It is concluded that the sodium selenite can be
employed with oxygen therapy and other supportive measures
in the management of brain tumor patients.
S-adenosyl-L-methionine a
counter to lead intoxication?
Paredes SR, Kozicki PA, Batlle AM.
Comp Biochem Physiol B 1985;82(4):751-7
The effect of S-adenosyl-L-methionine (SAM)
administration to both acute and chronic lead exposed mice
was investigated. SAM was given s.c. at different doses and
for different time intervals. The best results were
obtained using 20 mg SAM/kg applied daily over a period of
20-22 days. Results obtained in both acute and chronic lead
poisoning were quite similar. GSH concentration in blood
and liver, reduced in intoxicated animals was increased
after SAM administration reaching normal values. Blood,
liver and kidney lead content notably increased at the
beginning of SAM treatment and decreased rapidly in the
group receiving SAM, attaining values near control levels
in 2 weeks. A significant recovery of blood, liver, kidney,
spleen and brain delta-aminolevulic acid dehydratase
(ALA-D) initially reduced in poisoned animals, was clearly
produced after SAM administration. A clear and direct
correlation between the recovery of both ALA-D activity and
GSH levels and the decreased concentration of lead in
tissues was observed, reinforcing our proposal that
enhancement of thiol content as a result of SAM
administration would facilitate the detoxification process
and lead removal, consequently reversing the inactivation
of the enzyme. We conclude that SAM therapy is beneficial
in the treatment of lead intoxication.
Prevention by rutin of
gastric lesions induced by ethanol in rats: role of
endogenous prostaglandins.
Perez Guerrero C, Martin MJ, Marhuenda E. Departamento
de Farmacia y Tecnologia Farmaceutica, Laboratorio de
Farmacodinamia, Facultad de Farmacia, Universidad de
Sevilla, Spain.
Gen Pharmacol 1994 May;25(3):575-80
1. This study was designed to demonstrate the
cytoprotective effect of Rutin against ethanol-induced
gastric injury in rats and to determine whether this
cytoprotective effect is mediated by endogenous
prostaglandins. 100 and 200 mg/kg of Rutin given orally 1
hr before administration of 1 ml of 100% ethanol
significantly (p < 0.01) reduced the area of
macroscopic lesions induced by ethanol (84.16 +/- 23.01 and
54.75 +/- 16.05 respectively) when compared to distilled
water (305.60 +/- 67.20). However, it did not induce
changes in the amount and total proteins and hexosamines
content of gastric mucus. 2. Pretreatment with
indomethacin, 10 mg/kg s.c. 30 min before Rutin
administration, slightly but not significantly reduced the
cytoprotective effect. 3. The levels of PGE2 present in the
mucous material were not significantly modified with
administration of Rutin (100 mg/kg). 4. These results show
that Rutin has a cytoprotective effect against ethanol
injury in the rat, but this property does not appear to be
mediated by endogenous prostaglandins.
Antioxidant activity of
silybin in vivo during long-term iron overload in
rats.
Pietrangelo A, Borella F, Casalgrandi G, Montosi G,
Ceccarelli D, Gallesi D, Giovannini F, Gasparetto A, Masini
A. Dipartimento di Medicina Interna, University of Modena,
Italy.
Gastroenterology 1995 Dec;109(6):1941-9
BACKGROUND & AIMS: Hepatic iron toxicity may be
mediated by free radical species and lipid peroxidation of
biological membranes. The antioxidant property of silybin,
a main constituent of natural flavonoids, was investigated
in vivo during experimental iron overload. METHODS: Rats
were fed a 2.5% carbonyl-iron diet and 100 mg.kg body
wt-1.day-1 silybin for 4 months and were assayed for
accumulation of hepatic lipid peroxidation by-products by
immunocytochemistry, mitochondrial energy-dependent
functions, and mitochondrial malondialdehyde content.
RESULTS: Iron overload caused a dramatic accumulation of
malondialdehyde-protein adducts into iron-filled periportal
hepatocytes that was decreased appreciably by silybin
treatment. The same beneficial effect of silybin was found
on the iron-induced accumulation of malondialdehyde in
mitochondria. As to the liver functional efficiency,
mitochondrial energy wasting and tissue adenosine
triphosphate depletion induced by iron overload were
successfully counteracted by silybin. CONCLUSIONS: Oral
administration of silybin protects against iron-induced
hepatic toxicity in vivo. This effect seems to be caused by
the prominent antioxidant activity of this compound.
Antioxidant therapy in
the prevention of organ dysfunction syndrome and infectious
complications after trauma: early results of a prospective
randomized study.
Porter JM, Ivatury RR, Azimuddin K, Swami R. The Lincoln
Medical Center, Bronx, New York, U.S.A.
Am Surg 1999 May;65(5):478-83; erratum, Am Surg 1999
Sep;65(9):902
Reactive oxygen species have been implicated in the
etiology of multiorgan dysfunction syndrome and infectious
complications in trauma patients by either direct cellular
toxicity and/or the activation of intracellular signaling
pathways. Studies have shown that the antioxidant defenses
of the body are decreased in trauma patients; these include
glutathione, for which N-acetylcysteine is a precursor, and
selenium, which is a cofactor for glutathione. Eighteen
trauma patients were prospectively randomized to a control
or antioxidant group where they received N-acetylcysteine,
selenium, and vitamins C and E for 7 days. As compared with
the controls, the antioxidant group showed fewer infectious
complications (8 versus 18) and fewer organs dysfunctioning
(0 versus 9). There were no deaths in either group. We
conclude that these preliminary data may support a role for
the use of this antioxidant mixture to decrease the
incidence of multiorgan dysfunction syndrome and infectious
complications in the severely injured patient. This remains
to be confirmed in larger trials.
MSM: the multi-purpose
compound.
Prater G. Life Extension Magazine 1999 Sep;5(9):71-2
(http://www.lef.org/magazine/mag99/sep99-products.htm) Life
Extension Foundation, Ft. Lauderdale, FL. U.S.A.
No abstract available.
Vitamin E and heart
disease: basic science to clinical intervention
trials.
Pryor WA. The Biodynamics Institute, Louisiana State
University, Baton Rouge, LA 70803, U.S.A.
wpryor@LSU.edu
Free Radic Biol Med 2000 Jan 1;28(1):141-64
A review is presented of studies on the effects of
vitamin E on heart disease, studies encompassing basic
science, animal studies, epidemiological and observational
studies, and four intervention trials. The in vitro,
cellular, and animal studies, which are impressive both in
quantity and quality, leave no doubt that vitamin E, the
most important fat-soluble antioxidant, protects animals
against a variety of types of oxidative stress. The
hypothesis that links vitamin E to the prevention of
cardiovascular disease (CVD) postulates that the oxidation
of unsaturated lipids in the low-density lipoprotein (LDL)
particle initiates a complex sequence of events that leads
to the development of atherosclerotic plaque. This
hypothesis is supported by numerous studies in vitro, in
animals, and in humans. There is some evidence that the ex
vivo oxidizability of a subject's LDL is predictive of
future heart events. This background in basic science and
observational studies, coupled with the safety of vitamin
E, led to the initiation of clinical intervention trials.
The three trials that have been reported in detail are, on
balance, supportive of the proposal that supplemental
vitamin E can reduce the risk for heart disease, and the
fourth trial, which has just been reported, showed small,
but not statistically significant, benefits. Subgroup
analyses of cohorts from the older three trials, as well as
evidence from smaller trials, indicate that vitamin E
provides protection against a number of medical conditions,
including some that are indicative of atherosclerosis (such
as intermittent claudication). Vitamin E supplementation
also produces an improvement in the immune system and
protection against diseases other than cardiovascular
disease (such as prostate cancer). Vitamin E at the
supplemental levels being used in the current trials, 100
to 800 IU/d, is safe, and there is little likelihood that
increased risk will be found for those taking supplements.
About one half of American cardiologists take supplemental
vitamin E, about the same number as take aspirin. In fact,
one study suggests that aspirin plus vitamin E is more
effective than aspirin alone. There are a substantial
number of trials involving vitamin E that are in progress.
However, it is possible, or even likely, that each
condition for which vitamin E provides benefit will have a
unique dose-effect curve. Furthermore, different
antioxidants appear to act synergistically, so
supplementation with vitamin E might be more effective if
combined with other micronutrients. It will be extremely
difficult to do trials that adequately probe the
dose-effect curve for vitamin E for each condition that it
might affect, or to do studies of all the possible
combinations of other micronutrients that might act with
vitamin E to improve its effectiveness. Therefore, the
scientific community must recognize that there never will
be a time when the science is "complete." At some point,
the weight of the scientific evidence must be judged
adequate; although some may regard it as early to that
judgement now, clearly we are very close. In view of the
very low risk of reasonable supplementation with vitamin E,
and the difficulty in obtaining more than about 30 IU/day
from a balanced diet, some supplementation appears prudent
now.
Cysteine metabolism and
metal toxicity.
Quig D. Doctor's Data, Inc., West Chicago, IL, U.S.A.
dquig@doctorsdata.com
Altern Med Rev 1998 Aug;3(4):262-70
Chronic, low level exposure to toxic metals is an
increasing global problem. The symptoms associated with the
slow accumulation of toxic metals are multiple and rather
nondescript, and overt expression of toxic effects may not
appear until later in life. The sulfhydryl-reactive metals
(mercury, cadmium, lead, arsenic) are particularly
insidious and can affect a vast array of biochemical and
nutritional processes. The primary mechanisms by which the
sulfhydryl-reactive metals elicit their toxic effects are
summarized. The pro-oxidative effects of the metals are
compounded by the fact that the metals also inhibit
antioxidative enzymes and deplete intracellular
glutathione. The metals also have the potential to disrupt
the metabolism and biological activities of many proteins
due to their high affinity for free sulfhydryl groups.
Cysteine has a pivotal role in inducible, endogenous
detoxication mechanisms in the body, and metal exposure
taxes cysteine status. The protective effects of
glutathione and the metallothioneins are discussed in
detail. Basic research pertaining to the transport of toxic
metals into the brain is summarized, and a case is made for
the use of hydrolyzed whey protein to support metal
detoxification and neurological function. Metal exposure
also affects essential element status, which can further
decrease antioxidation and detoxification processes. Early
detection and treatment of metal burden is important for
successful detoxification, and optimization of nutritional
status is paramount to the prevention and treatment of
metal toxicity.
The effects of
glutathione depletion on reproductive success in oysters,
Crassostrea virginica.
Ringwood AH, Conners DE. Marine Resources Research
Institute, 217 Fort Johnson Road, Charleston, SC 29412,
U.S.A. ringwooda@mrd.dnr.state.sc.us
Mar Environ Res 2000 Jul-Dec;50(1-5):207-11
Glutathione (GSH) is a ubiquitous tripeptide that
functions as a very important modulator of cellular
homeostasis, including detoxification of metals and
oxyradicals. Therefore, depletion of GSH may predispose
organisms to pollutant stress. Reproductively active
oysters (Crassostrea virginica) were exposed to buthionine
sulfoximine in the laboratory to deplete gonadal GSH. The
effects of metal exposures (Cd and Cu) on fertilization and
developmental assays were evaluated using gametes from
control and GSH-depleted adults. Fertilization success was
not affected by GSH status, i.e. the fertilization rates of
gametes derived from GSH-depleted adults were the same or
slightly higher. However, GSH depletion did increase the
susceptibility of developing embryos to metal toxicity,
i.e. adverse effects on embryonic development were observed
at lower metal concentrations with gametes derived from
GSH-depleted adults. These effects may be related to
diminished removal of free radicals or increased
availability of metals. Whereas sperm penetration of
embryonic membranes and fertilization success may be
facilitated by free radicals, the persistence of free
radicals during subsequent developmental periods may
adversely affect differentiation and normal development.
GSH probably also plays an important role in scavenging
toxic metals and reducing metal interactions with essential
developmental processes. These results suggest that
parental depletion of GSH may increase the susceptibility
of embryos to metal toxicity.
Metal toxicity in
children.
Roberts JR. June 1999 Training Manual on Pediatric
Environmental Health: Putting It into Practice.
(http://www.cehn.org/cehn/trainingmanual/pdf/manual-full.pdf)
Children's Environmental Health Network, Emeryville, CA,
U.S.A.
No abstract available.
Long-term use of
nicotine chewing gum and mercury exposure from dental
amalgam fillings.
Sallsten G, Thoren J, Barregard L, Schutz A, Skarping G.
Department of Occupational Medicine, Sahlgrenska University
Hospital, Goteborg, Sweden.
J Dent Res 1996 Jan;75(1):594-8
In experimental studies, chewing gum has been shown to
increase the release rate of mercury vapor from dental
amalgam fillings. The aim of the present study was to
investigate the influence of long-term frequent chewing on
mercury levels in plasma and urine. Mercury levels in
plasma (P-Hg) and urine (U-Hg), and urinary cotinine were
examined in 18 subjects who regularly used nicotine chewing
gum, and in 19 referents. Age and number of amalgam
surfaces were similar in the two groups. Total mercury
concentrations in plasma and urine were determined by means
of cold vapor atomic absorption spectrometry. Urinary
cotinine was determined by gas chromatography-mass
spectrometry. The chewers had been using 10 (median) pieces
of gum per day for the past 27 (median) months. P-Hg and
U-Hg levels were significantly higher in the chewers (27
nmol/L and 6.5 nmol/mmol creatinine) than in the referents
(4.9 nmol/L and 1.2 nmol/mmol creatinine). In both groups,
significant correlations were found between P-Hg or U-Hg on
the one hand and the number of amalgam surfaces on the
other. In the chewers, no correlations were found between
P-Hg or U-Hg and chewing time per day or cotinine in urine.
Cotinine in urine increased with the number of pieces of
chewing gum used. The impact of excessive chewing on
mercury levels was considerable.
Alzheimer's disease,
dental amalgam and mercury.
Saxe SR, Wekstein MW, Kryscio RJ, Henry RG, Cornett CR,
Snowdon DA, Grant FT, Schmitt FA, Donegan SJ, Wekstein DR,
Ehmann WD, Markesbery WR. Geriatric Oral Health Program,
College of Dentistry, University of Kentucky, Lexington,
KY, U.S.A.
J Am Dent Assoc 1999 Feb;130(2):191-9
BACKGROUND: Mercury, or Hg, is a neurotoxin that has
been speculated to play a role in the pathogenesis of
Alzheimer's disease, or AD. Dental amalgam releases low
levels of Hg vapor and is a potential source of Hg for a
large segment of the adult population. METHODS: The authors
studied 68 subjects with AD and 33 control subjects without
AD to determine Hg levels in multiple brain regions at
autopsy and to ascertain the subjects' dental amalgam
status and history. The subjects were from central Kentucky
and Elm Grove, Wis. The authors conducted dental amalgam
assessments during the lives of the majority of subjects
and in some subjects at the time of autopsy only. The
authors also determined three dental amalgam index
scores--Event (placement, repair or removal of amalgam),
Location and Time In Mouth--in addition to the numbers of
and surface area of occlusal amalgam restorations. The
authors determined Hg levels in multiple brain regions and
performed full neuropathologic evaluations to confirm the
normal status of the brain or the presence of AD. RESULTS:
The authors found no significant association of AD with the
number, surface area or history of having dental amalgam
restorations. They also found no statistically significant
differences in brain Hg level between subjects with AD and
control subjects. CONCLUSIONS: Hg in dental amalgam
restorations does not appear to be a neurotoxic factor in
the pathogenesis of AD. The authors found that brain Hg
levels are not associated with dental amalgam, either from
existing amalgam restorations or according to subjects'
dental amalgam restoration history. CLINICAL IMPLICATIONS:
Dental amalgam restorations, regardless of number, occlusal
surface area or time, do not relate to brain Hg levels.
Effect of selenium on
the side effect profile of adjuvant
chemotherapy/radiotherapy in patients with breast
carcinoma. Design for a clinical study.] [Article
in German]
Schumacher K.
Med Klin 1999 Oct 15;94 Suppl 3:45-8
Selenium is a very important component of the
antioxidative protective mechanism which belongs to every
cell. By chemotherapy and radiotherapy a strong increase of
free oxygen radicals is induced leading to damage also of
normal tissue. This phenomenon is registered as adverse
drug reactions. Since, in addition, tumor patients
frequently have low selenium blood levels the application
of higher doses of selenium in connection with chemo- and
radiotherapy will induce the toxicity of the treatment
without lowering the efficiency. Within the presented
prospective randomized placebo-controlled double-blind
phase-III study we intend to answer the question whether
the application of higher doses of sodium selenite will
reduce the toxicity of chemotherapy and radiotherapy.
Primary targets of the study are therefore the evaluation
of toxicity according to CTC-criteria and of life
quality.
Dependence of
cadmium-metallothionein nephrotoxicity on
glutathione.
Shaikh ZA, Northup JB, Vestergaard P. Department of
Biomedical Sciences, College of Pharmacy, University of
Rhode Island, Kingston, RI 02881-0809, U.S.A.
ZShaikh@uri.edu
J Toxicol Environ Health A 1999 Jun 11;57(3):211-22
Acute cadmium-metallothionein (CdMT) injection is
frequently used as a model to study the mechanism of
chronic Cd-induced nephrotoxicity. The purpose of this
study was to investigate the relationship between
glutathione (GSH) status and the ability of CdMT, either
administered as a bolus dose or infused over a 24-h period
by an osmotic minipump, to cause nephrotoxicity. GSH levels
were modulated by pretreatment with either buthionine
sulfoximine (BSO) or GSH. BSO enhanced while GSH suppressed
acute CdMT nephrotoxicity. An infused dose of CdMT (150
microg Cd/kg) that was well tolerated when delivered over a
24-h period became nephrotoxic when GSH synthesis was
inhibited by BSO. With depletion of GSH, as little as 0.4
microg Cd/g renal cortex was sufficient to cause
nephrotoxicity after an acute dose of CdMT. While BSO had
no effect on renal Cd accumulation, pretreatment with GSH
reduced renal cortical Cd accumulation by 36%. CdMT
nephrotoxicity was enhanced by depleting renal GSH, but
without increasing renal Cd accumulation, which suggests
that intracellular GSH is directly involved in protection
against CdMT nephrotoxicity. Reduced Cd accumulation in the
renal cortex following GSH pretreatment suggests an
additional extracellular mechanism of GSH protection. It is
concluded that GSH status is an important determinant of
CdMT nephrotoxicity, with low GSH levels enhancing and high
GSH levels reducing its toxicity, and that the mechanism
appears to involve both intracellular and extracellular
sites.
Protection against
chronic cadmium toxicity by glycine.
Shaikh ZA, Tang W. Department of Biomedical Sciences,
University of Rhode Island, Kingston, RI 02881, U.S.A.
zshaikh@uriacc.uri.edu
Toxicology 1999 Feb 15;132(2-3):139-46
A Japanese drug containing glycine, glycyrrhizin, and
cysteine (Stronger Neo-Minophagen C) has been reported to
protect against chronic cadmium (Cd) toxicity. The present
study was conducted to evaluate which of the three
constituents of this drug was the main antagonist for Cd
toxicity and whether the mechanism of protection involved
antioxidant action. Adult female Sprague-Dawley rats were
injected sc with 5 micromol CdCl2/kg per day, five times
per week, for 15 weeks. Four groups of Cd-injected animals
received co-treatments with either 10 mg glycyrrhizin/kg,
100 mg glycine/kg, 5 mg cysteine/kg, or with a mixture of
all three compounds, five times per week, starting from
week 7. An additional Cd-injected group was co-treated with
vitamin E (100 mg/kg, five times per week, starting from
week 7) as a positive control. Only those animals that
received vitamin E, Minophagen mixture, or glycine were
protected against Cd-induced hepatotoxicity as well as
nephrotoxicity. All three co-treatments suppressed
Cd-induced hepatic and renal lipid peroxidation. We
conclude that the reported beneficial effects of Stronger
Neo-Minophagen C are due to glycine, which appears to
protect against chronic Cd toxicity by reducing oxidative
stress.
Glutathione status and
cadmium neurotoxicity: studies in discrete brain regions of
growing rats.
Shukla GS, Srivastava RS, Chandra SV. Industrial
Toxicology Research Centre, Lucknow, India.
Fundam Appl Toxicol 1988 Aug;11(2):229-35
Intraperitoneal administration of cadmium (Cd2+, 0.4
mg/kg) daily for 30 days to rats was found to decrease the
contents of reduced glutathione (GSH) and increase oxidized
glutathione (GSSG) in various brain regions. These changes
resulted in a significant decline in the GSH/GSSG ratio in
different brain regions, except for the hippocampus and
midbrain. In addition, the activities of glutathione
reductase (GR) and glucose-6-phosphate dehydrogenase (GPDH)
were also significantly inhibited in different brain
regions. Measurement of regional Cd levels revealed that Cd
administration significantly increased the levels in all
brain regions except for the hippocampus, which could be
the reason for not finding any change in any of the
biochemical parameters studied in this region. The observed
changes in the regional GSH/GSSG ratios could be the result
of inhibition in GR activity, as this enzyme catalyzes an
irreversible conversion of GSH to GSSG and is responsible
for higher cellular GSH levels. GR uses NADPH in its
reaction; therefore, the inhibition of GPDH may further
aggravate the situation because of the short supply of
NADPH. The alterations in the regional "glutathione status"
may affect various related metabolic processes, including
those required for detoxification of lipid peroxides which
have recently been suggested to play a role in the
mechanism of Cd neurotoxicity.
Effect of chronic
cadmium exposure on glutathione S-transferase and
glutathione peroxidase activities in rhesus monkey: the
role of selenium. Sidhu M, Sharma M, Bhatia M,
Awasthi YC, Nath R. Department of Biochemistry,
Postgraduate Institute of Medical Education and Research,
Chandigarh, India.
Toxicology 1993 Oct 25;83(1-3):203-13
The effect of cadmium (Cd) on the activity of
glutathione S-transferase (GST) and glutathione peroxidase
(GSH-Px) which play an important role in the detoxification
of xenobiotics, was studied in the liver, kidney, heart and
lung of Rhesus monkeys. Furthermore, the role of selenium
(Se) in the modulation of Cd toxicity with respect to GST
and GSH-Px was also evaluated. Cadmium exposure (5 mg Cd/kg
body wt./day as CdCl2 for 10 weeks) to monkeys resulted in
decreased GSH-Px activity in all four organs present in the
order liver > kidney > heart > lung.
Cadmium administration also resulted in a significant
decrease in total GST activity present in the order liver
> heart > kidney > lung, whereas a
significant increase in the pi class GST activity was
observed greatest in the heart followed by lung, kidney and
liver. Oral administration of Se (0.5 mg Se/kg body wt./day
as Na2SeO3 for 10 weeks) caused a significant increase in
GSH-Px activity in the order liver > heart >
kidney > lung. Selenium administration caused an
increase in total GST activity in liver and lung but a
decrease in kidney and heart. Simultaneous administration
of Cd and Se resulted in an increase in total GST activity
(except in lung) including the pi class activity as well as
GSH-Px activity in all four tissues under study. Thus, the
mechanism by which selenium decreases Cd toxicity in Rhesus
monkeys, seems to rely on the protection of the enzyme
systems GST and GSH-Px in the four organs, possibly by
forming non-toxic cadmium selenide.
Activities of silymarin
and its flavonolignans upon low density lipoprotein
oxidizability in vitro.
Skottova N, Krecman V, Simanek V. Institute of Medical
Chemistry, Medical Faculty, Palacky University, Hnevotinska
3, 775 15 Olomouc, Czech Republic.
Phytother Res 1999 Sep;13(6):535-7
Silymarin, a standardized extract from Silybum marianum,
inhibited in vitro the copper- nduced oxidation of human
LDL in a concentration-dependent manner. Silybin, a main
flavonolignan of silymarin, appeared to be responsible for
this LDL antioxidant effect. Silychristin and silydianin,
other flavonolignans of silymarin, acted rather as pro-
oxidants, but with regard to their content in silymarin, it
did not contribute significantly to the reduction of the
total LDL antioxidant capacity of silymarin. Copyright 1999
John Wiley & Sons, Ltd.
Case report of metallic
mercury injury.
Smith SR, Jaffe DM, Skinner MA. Department of Pediatric
Emergency Medicine, St. Louis Children's Hospital,
Washington University School of Medicine, St. Louis, MO
63110-1077, U.S.A.
Pediatr Emerg Care 1997 Apr;13(2):114-6
OBJECTIVE: Injury and poisoning from metallic mercury
has become a rare event. Review of the literature and a
case report of pediatric metallic mercury injury are
presented. DESIGN: A case report. SETTING: The Emergency
Department at St. Louis Children's Hospital. PATIENTS OR
PARTICIPANTS: A 15-year-old boy. INTERVENTIONS: None. MAIN
OUTCOME MEASURES: None. RESULTS: The 15-year-old boy fell
on a broken mercury thermometer. A subcutaneous abscess
formed on his left forearm during the next five days. He
had no signs or symptoms of mercury toxicity. His wound was
debrided in the operating room and healed completely after
several months. CONCLUSIONS: This case shows elemental
mercury from a thermometer as a potential, if unusual,
source of mercury toxicity.
Carcinogen binding to
various types of dietary fiber.
Smith-Barbaro P, Hanson D, Reddy BS.
J Natl Cancer Inst 1981 Aug;67(2):495-7
The percent of the carcinogen 1,2-dimethylhydrazine
(DMH) bound to a variety of fibers, such as wheat bran,
corn bran, citrus pulp, citrus pectin, and alfalfa, was
examined at pH values ranging from 1 to 12. The percent of
DMH bound to wheat bran increased from 4% at PH 1 to 55% at
pH 2 to 77% at pH 12. A sharp rise in carcinogen binding to
corn bran occurred between pH 5% of the DMH was bound and
pH 8 where 51% of the DMH was bound. The percent of DMH
bound to dehydrated citrus pulp also increased as the pH
increased with 10% binding observed at pH 1 and with 57%
binding observed at pH 12. Between pH 2 and pH 7, the
percent of DMH bound to pectin decreased from 60 to 11%. As
the pH became more basic, the percent of DMH bound to
pectin increased to 42% at pH 12. The sharpest rise in the
percent of DMH bound to alfalfa meal occurred between pH
10.5 and pH 12.0. Results from this experiment showed that
the affinity to various types of dietary fibers for the
colon carcinogen DMH was differentially affected by pH.
These results suggested that the protective effect of
certain types of dietary fiber against chemically induced
colon cancer my in part be attributed to enhanced
carcinogen binding by dietary fiber in the colon.
Stimulatory effect of
Silibinin on the DNA synthesis in partially hepatectomized
rat livers: non-response in hepatoma and other malign cell
lines.
Sonnenbichler J, Goldberg M, Hane L, Madubunyi I, Vogl
S, Zetl I.
Biochem Pharmacol 1986 Feb 1;35(3):538-41
No abstract available.
Stimulatory effects of
silibinin and silicristin from the milk thistle Silybum
marianum on kidney cells.
Sonnenbichler J, Scalera F, Sonnenbichler I, Weyhenmeyer
R. Max Planck Institute for Biochemistry, Martinsried,
Germany.
J Pharmacol Exp Ther 1999 Sep;290(3):1375-83
The biochemical influence of flavonolignans from the
milk thistle Silybum marianum has been tested on kidney
cells of African green monkeys. Two nonmalignant cell lines
were selected, with the focus of the work on the
fibroblast-like Vero line. Proliferation rate, biosynthesis
of protein and DNA, and the activity of the enzyme lactate
dehydrogenase (as a measure of the cellular metabolic
activity) were chosen as parameters for the effect of the
flavonolignans. Silibinin and silicristin show remarkable
stimulatory effects on these parameters, mainly in Vero
cells; however, isosilibinin and silidianin proved to be
inactive. In vitro experiments with kidney cells damaged by
paracetamol, cisplatin, and vincristin demonstrated that
administration of silibinin before or after the
chemical-induced injury can lessen or avoid the nephrotoxic
effects. The results warrant in vivo evaluations of the
flavonolignan derivatives.
[Evaluation of the
antiradical protector effect of multifermented milk serum
with reiterated dosage in rats.] [Article in
French]
Stella V, Postaire E. Direction Scientifique, Pharmacie
Centrale des Hopitaux, Paris.
C R Seances Soc Biol Fil 1995;189(6):1191-7
Epidemiological and experimental studies suggest that
dietary milk products may exert an inhibitory effect on the
development of several types of tumors. Some recent
experiments in rodents indicate that the antitumor activity
of the dairy product is in the protein fraction and more
specifically in the whey protein component of milk. It has
been demonstrated that whey protein diets result in
increased glutathione (GSH) concentration in a number of
tissues, and that some of the beneficial effects of whey
protein intake are abrogated by inhibition of GSH
synthesis. Whey protein is particularly rich in substrates
for GSH synthesis. It has been suggested that whey protein
may be exerting its effect on carcinogenesis and VIH
infection by enhancing GSH concentration. Lactoferrin, one
of the proteins contained in whey has aise been studied in
this way. It has been suggested that lactoferrin binding
may play an important role in maintaining, optimal
mononuclear phagocyte function, thus protecting adjacent
tissue against phagocyte derived radicals. Moreover it has
been demonstrated by one of us that the level of plasma
lactoferrin were decreased in HIV-1 infected patients in
relation to the progression of the disease. The aim of the
present study is to evaluate in rat the reactive oxygen
species, scavenger activities (ROSSA) of red blood cells
(RBCs) with a multifermented whey (SK 344), by repeated
doses during 16 days. This study has permitted to
demonstrate in vivo that the SK 344 has an excellent ROSSA
corresponding to a limitation of the lipoperoxidation of
RBCs membranes by singlet oxygen and nitric oxide. We can
conclude that whey protein, lactoferrin and multifermented
whey are good candidates as dietary inhibitors of the
oxidative stress and should be considered as potential
medicinal foods in various pathologies as HIV infection and
cancer.
Restoration of the
cellular thiol status of peritoneal macrophages from CAPD
patients by the flavonoids silibinin and
silymarin.
Tager M, Dietzmann J, Thiel U, Hinrich Neumann K,
Ansorge S. Institute of Immunology, Otto-von-Guericke
University, Leipziger Str. 44 D-39120 Magdeburg, Germany.
michael.tager@medizin.uni-magdeburg.de
Free Radic Res 2001 Feb;34(2):137-51
During continuous ambulatory peritoneal dialysis (CAPD)
the peritoneal immune ells, mainly macrophages, are highly
compromised by multiple factors including oxidative stress,
resulting in a loss of functional activity. One reason for
the increase of inflammatory reactions could be an
imbalance in the thiol-disulfide status. Here, the possible
protective effects of the antioxidant flavonoid complex
silymarin and its major component silibinin on the cellular
thiol status were investigated. Peritoneal macrophages from
dialysis fluid of 30 CAPD patients were treated with
silymarin or silibinin up to 35 days. A time-dependent
increase of intracellular thiols was observed with a nearly
linear increment up to 2.5-fold after 96 hours, reaching a
maximum of 3.5-fold after 20 days of culture.
Surface-located thiols were also elevated. The
stabilization of the cellular thiol status was followed by
an improvement of phagocytosis and the degree of maturation
as well as significant changes in the synthesis of IL-6 and
IL-1ra. Furthermore, the treatment of peritoneal
macrophages with flavonoids in combination with cysteine
donors resulted in a shortened and more efficient time
course of thiol normalization as well as in a further
increased phagocytosis. In addition, GSH-depletion in
thiol-deficient media simulating CAPD procedures led to
intracellular thiol deficiency similar to the in vivo
situation. It is concluded that treatment with milk thistle
extracts silymarin and silibinin alone or, more effectively
in combination with cysteine donors, provide a benefit for
peritoneal macrophages of CAPD-patients due to a
normalization and activation of the cellular thiol status
followed by a restoration of specific functional
capabilities.
Preventive effect of
vitamin E in cadmium intoxication.
Tandon SK, Singh S, Dhawan M. Industrial Toxicology
Research Centre, Lucknow, India.
Biomed Environ Sci 1992 Mar;5(1):39-45
The influence of vitamin E on cadmium intoxication was
investigated in rats. The exposure to cadmium (1 mg/kg, Cd
as CdCl2.2H2O, intraperitoneally for 7 days) decreased the
activity of hepatic and renal glutamic oxalacetic and
glutamic pyruvic transaminases (GOT, GPT) and alkaline
phosphatase (ALP) accompanied by increase in the levels of
serum GOT and GPT and urinary protein. Simultaneous
administration of vitamin E (5 mg/kg, intramuscularly for 7
days) reduced these Cd induced biochemical alterations. The
accumulation of Cd in blood, liver and kidney also
decreased significantly upon co-exposure to vitamin E. The
antioxidant property of vitamin E seems to be responsible
for the observed protection of Cd intoxication. Nephrotoxicity of
cadmium-metallothionein: protection by zinc and role of
glutathione.
Tang W, Sadovic S, Shaikh ZA. College of Pharmacy,
University of Rhode Island, Kingston, RI 02881, U.S.A.
Toxicol Appl Pharmacol 1998 Aug;151(2):276-82
Chronic cadmium (Cd) exposure can cause renal proximal
tubular dysfunction resulting from the release of Cd
metallothionein (CdMT) from the liver and its accumulation
and degradation in the renal tubular epithelial cells.
Pretreatment with zinc (Zn) can protect against acute CdMT
nephrotoxicity. While induction of MT by Zn plays a part in
Zn protection, other factors, such as glutathione (GSH),
may also be involved because protection is offered even in
MT-null mice. The present study was designed to investigate
the involvement of GSH in Zn protection against acute CdMT
nephrotoxicity. The study was carried out in MT-null mice
to remove the induction of MT by Zn as a confounding
variable. Three approaches were used to modulate renal
cortex GSH levels: buthionine sulfoximine (BSO) was
administered to inhibit GSH synthesis, and GSH and Zn were
administered to increase the GSH levels. Both GSH and Zn
were effective in protecting against CdMT nephrotoxicity.
Elevation in renal cortex GSH levels, however, was not
essential for Zn protection, as a low dose of Zn that
caused no significant increase in renal GSH also protected
against CdMT. On the other hand, maintenance of normal GSH
status was essential for Zn protection, as inhibition of
GSH synthesis abolished this protection. Both GSH and Zn
reduced the accumulation of Cd as well as MT in the renal
cortex, with Zn causing greater reduction in Cd
accumulation than that of MT. The relative intracellular
distribution of Cd was unaltered. These results suggest
that in MT-null mice Zn protects against CdMT
nephrotoxicity by possibly displacing some of the Cd from
CdMT as well as reducing the uptake of CdMT, and that this
protection requires the maintenance of normal GSH status.
Copyright 1998 Academic Press.
Association of
glutathione S-transferase isozyme-specific induction and
lipid peroxidation in two inbred strains of mice subjected
to chronic dietary iron overload.
Tjalkens RB, Valerio LG Jr, Awasthi YC, Petersen DR.
Department of Pharmaceutical Sciences, University of
Colorado Health Sciences Center, Denver, CO 80262,
U.S.A.
Toxicol Appl Pharmacol 1998 Jul;151(1):174-81
The alpha-class glutathione S-transferases are proposed
to play a prominent role in catalyzing the conjugation of
glutathione with electrophilic aldehydic products of lipid
peroxidation. The effect of iron-induced lipid peroxidation
on induction of glutathione S-transferase (GST) isozymes A1
and A4 in the livers of male C57/BL6Ibg and DBA/J2Ibg mice
was studied. C57 and DBA mice were fed for 4 months on a
diet supplemented with iron as ferrocene and then were
assessed for liver injury, hepatic iron loading, indices of
lipid peroxidation, GST activity, and induction of GST
isozymes A1 and A4. Iron-treated animals displayed a loss
in body weight from pair-fed controls and had large
increases in hepatic non-heme iron with concomitant liver
injury, as measured by serum alanine aminotransferase.
Hepatic lipid hydroperoxides, a direct measure of oxidized
membrane lipids, were significantly increased only in C57
mice, but hepatic concentrations of reduced glutathione
(GSH) were significantly increased in both inbred strains.
Total GST activity toward 1-chloro-2,4-dinitrobenzene was
significantly increased in C57 mice but not in DBA. Western
blot studies using polyclonal antibodies specific for GST
A1 and A4 revealed significant increases of 1.5-2.0-fold in
these GST isoforms in both inbred strains. These results in
a unique murine model for hepatic iron overload further
support recent in vivo studies (Khan et al., Toxicol. Appl.
Pharmacol., 131, 63-72, 1995) that have associated
induction of GST A4 with protection against oxidative
stress-induced lipid peroxidation. The observed increases
in lipid hydroperoxides, hepatic GSH, GST activity, and GST
A1 and A4 protein strongly support the hypothesis that
induction of GST A1 and A4 represents an important
protective event in the detoxification of electrophilic
products of lipid peroxidation. Copyright 1998 Academic
Press.
ToxFAQs™ for
Aluminum. CAS 7429-90-5.
Agency for Toxic Substances and Disease Registry. June
1999 Division of Toxicology, 1600 Clifton Road NE, Mailstop
E-29, Atlanta, GA 30333, U.S.A.
HIGHLIGHTS: Everyone is exposed to low levels of
aluminum from food, air, and water. Exposure to high levels
of aluminum may result in respiratory problems. Aluminum
has been found in at least 427 of the 1,467 National
Priorities List sites identified by the Environmental
Protection Agency (EPA).
ToxFAQs™ for
Arsenic. CAS 7440-38-2.
Agency for Toxic Substances and Disease Registry. July
2001 Division of Toxicology, 1600 Clifton Road NE, Mailstop
E-29, Atlanta, GA 30333, U.S.A.
HIGHLIGHTS: Exposure to higher than average levels of
arsenic occurs mostly in the workplace, near hazardous
waste sites, or in areas with high natural levels. At high
levels, inorganic arsenic can cause death. Exposure to
lower levels for a long time can cause a discoloration of
the skin and the appearance of small corns or warts.
Arsenic has been found at 1,014 of the 1,598 National
Priority List sites identified by the Environmental
Protection Agency (EPA).
ToxFAQs™ for
Cadmium. CAS 7440-43-9.
Agency for Toxic Substances and Disease Registry. June
1999 Division of Toxicology, 1600 Clifton Road NE, Mailstop
E-29, Atlanta, GA 30333, U.S.A.
HIGHLIGHTS: Exposure to cadmium happens mostly in the
workplace where cadmium products are made. The general
population is exposed from breathing cigarette smoke or
eating cadmium contaminated foods. Cadmium damages the
lungs, can cause kidney disease, and may irritate the
digestive tract. This substance has been found in at least
776 of the 1,467 National Priorities List sites identified
by the Environmental Protection Agency (EPA).
ToxFAQs™ for
Lead. CAS 7439-92-1.
Agency for Toxic Substances and Disease Registry. June
1999 Division of Toxicology, 1600 Clifton Road NE, Mailstop
E-29, Atlanta, GA 30333, U.S.A.
HIGHLIGHTS: Exposure to lead can happen from breathing
workplace air or dust, eating contaminated foods, or
drinking contaminated water. Children can be exposed from
eating lead-based paint chips or playing in contaminated
soil. Lead can damage the nervous system, kidneys, and
reproductive system. Lead has been found in at least 1,026
of 1,467 National Priorities List sites identified by the
Environmental Protection Agency (EPA).
ToxFAQs™ for
Mercury. CAS 7439-97-6.
Agency for Toxic Substances and Disease Registry. April
1999 Division of Toxicology, 1600 Clifton Road NE, Mailstop
E-29, Atlanta, GA 30333, U.S.A.
HIGHLIGHTS: Exposure to mercury occurs from breathing
contaminated air, ingesting contaminated water and food,
and having dental and medical treatments. Mercury, at high
levels, may damage the brain, kidneys, and developing
fetus. This chemical has been found in at least 714 of
1,467 National Priorities List sites identified by the
Environmental Protection Agency.
Effects of some thiol
chelators on enzymatic activities in blood, liver and
kidneys of acute arsenic (III) exposed mice.
Tripathi N, Flora SJ. Division of Pharmacology and
Toxicology, Defence Research and Development Establishment,
Gwalior, India. Biomed Environ Sci 1998 Mar;11(1):38-45
The effects of meso 2, 3-dimercaptosuccinic acid (DMSA),
sodium 2, 3-dimercaptopropane 1-sulfonate (DMPS) and
S-adenosyl L-methionine (SAM) on the enzymatic activities
of mice were studied. The mice were given intraperitoneal
(i.p.) injections of these chelating agents (1 mmol/kg) and
3 h later the activity of delta-aminolevulinic acid
dehydratase (ALAD) in the blood, and aspartate
aminotransferase (AST), alanine aminotransferase (ALT),
gamma-glutamyltranspeptidase (gamma-GT), alkaline
phosphatase (ALP) in the liver and kidney were determined.
The activity of blood ALAD was significantly increased by
the administration of DMSA and SAM while DMPS had only a
moderate effect. The activities of other hepatic enzymes
changed little when the mice were treated with these
chelating agents, except for a significant reduction in
hepatic ALP activity following DMPS administration. Arsenic
(III) administration markedly increased the activities of
ALT and ALP in the liver and kidneys. The changes in the
enzymatic activities by treatment with arsenic were
prevented by injection of DMSA, DMPS and SAM, DMSA being
the most effective. These results indicate that DMSA, DMPS
and SAM were not toxic to the liver or kidneys of mice and
that treatment with DMSA is more effective than DMPS or SAM
in protecting mice from acute hepatic or renal toxicity
caused by arsenic.
Serum selenium and
glutathione-peroxidase activities and their interaction
with toxic metals in dialysis and renal transplantation
patients.
Turan B, Delilbasi E, Dalay N, Sert S, Afrasyap L, Sayal
A. Department of Biophysics, Faculty of Medicine, Ankara
University, Turkiye. Biol Trace Elem Res 1992
Apr-Jun;33:95-102
Selenium, aluminum, cadmium, and magnesium
concentrations and glutathione-peroxidase activities in
sera of 35 healthy individuals, 30 renal transplants, and
30 hemodialysis patients were measured. Serum selenium,
aluminum, and cadmium concentrations in both groups of
patients were higher than the controls (p less than 0.001),
whereas the serum glutathione-peroxidase levels were lower
(p less than 0.001). According to our results, it can be
concluded that the patients receiving hemodialysis are
subjected to more toxic elements than the transplantation
patients. These findings imply that dietary selenium
supplement may be suggested in renal failure for the
detoxification of elements, such as cadmium and mercury.
The essential trace element selenium takes part not only in
the direct protection of endothelial cells against the
accumulation of aggressive oxygen species, but also in the
prevention of the toxic effects of cadmium or in the
modulation of the active calcium transport.
Deferoxamine
(Systemic).
USNLM/NIH (no authors given). 2001 Drug Information
(http://www.nlm.nih.gov/medlineplus/druginfo). U.S.
National Laboratory of Medicine/National Institutes of
Health, Bethesda, MD, U.S.A.
(http://www.nlm.nih.gov/medlineplus/druginfo)
No abstract available.
DMSA (Succimer
Systemic).
USNLM/NIH (no authors given). 2001 Drug Information
(http://www.nlm.nih.gov/medlineplus/druginfo). U.S.
National Laboratory of Medicine/National Institutes of
Health, Bethesda, MD, U.S.A.
(http://www.nlm.nih.gov/medlineplus/druginfo)
No abstract available.
EDTA (Edetate Disodium
Systemic).
USNLM/NIH (no authors given). 2001 Drug Information
(http://www.nlm.nih.gov/medlineplus/druginfo). U.S.
National Laboratory of Medicine/National Institutes of
Health, Bethesda, MD, U.S.A.
(http://www.nlm.nih.gov/medlineplus/druginfo)
No abstract available.
Penicillamine
(Systemic).
USNLM/NIH (no authors given). 2001 Drug Information
(http://www.nlm.nih.gov/medlineplus/druginfo). U.S.
National Laboratory of Medicine/National Institutes of
Health, Bethesda, MD, U.S.A.
Biochemical bases of
the pharmacological action of the flavonoid silymarin and
of its structural isomer silibinin.
Valenzuela A, Garrido A. Unidad de Bioquimica
Farmacologica y Lipidos, Universidad de Chile, Santiago.
Biol Res 1994;27(2):105-12
The flavonoid silymarin and one its structural
components, silibinin, have been well characterized as
hepato-protective substances. However, little is known
about the biochemical mechanisms of action of these
substances. This review deals with recent investigations to
elucidate the molecular action of the flavonoid. Three
levels of action have been proposed for silymarin in
experimental animals: a) as an antioxidant, by scavenging
prooxidant free radicals and by increasing the
intracellular concentration of the tripeptide glutathione;
b) regulatory action of the cellular membrane permeability
and increase of its stability against xenobiotic injury; c)
at the nuclear expression, by increasing the synthesis of
ribosomal RNA by stimulating DNA polymerase I and by
exerting a steroid-like regulatory action on DNA
transcription. The specific hepatoprotective action of
silibinin against the toxicity of ethanol, phenylhydrazine
and acetaminophen is also discussed. It is suggested that
the biochemical effects observed for the flavonoid in
experimental models may settle the basis for understanding
the pharmacological action of silymarin and silibinin.
Induction of lesions of
selenium-vitamin E deficiency in ducklings fed silver,
copper, cobalt, tellurium, cadmium, or zinc: protection by
selenium or vitamin E supplements.
Van Vleet JF, Boon GD, Ferrans VJ. Am J Vet Res 1981
Jul;42(7):1206-17
In 3 experiments, 684 newly hatched White Pekin
ducklings were fed (for 15 to 28 days) a commercial starter
mash that was adequate in selenium and vitamin E (Se-E)
content, either alone or with supplements of Ag (3,000
mg/kg of feed, as acetate), Cu (1,500 mg/kg, as sulfate),
Co (200 or 500 mg/kg, as chloride), Te (500 mg/kg, as
tetrachloride), Cd (100 or 500 mg/kg, as sulfate), Zn
(3,000 or 6,000 mg/kg, as sulfate), or V (100 mg/kg, as
vanadate). The ducklings fed Ag, Cu, Co, Te, Cd, and Zn
frequently developed lesions characteristic of Se-E
deficiency, such as necrosis of skeletal and cardiac muscle
and of smooth muscle of the gizzard and intestine. Complete
protection from the muscle lesions produced by Cu, Co, Te,
Cd, and Zn supplements was provided by vitamin E (200 IU of
alpha-tocopherol acetate/kg) and Se (2 mg/kg, as selenite).
Ducklings fed Ag were protected by supplements of vitamin E
and partial protection was achieved by Se addition. The
birds fed excessive Zn developed pancreatic necrosis and
fibrosis that was not prevented by supplements of Se or
vitamin E. Terminally, blood glutathione peroxidase
activity was low and hepatic Se concentration was increased
in the ducklings fed Ag. However, neither blood glutathione
peroxidase activity nor hepatic Se concentrations were
consistently abnormal in ducklings fed other trace
elements, although lesions of Se-E deficiency were often
present in these animals.
Lead induced disorders
in hematopoietic and drug metabolizing enzyme system and
their protection by ascorbic acid
supplementation.
Vij AG, Satija NK, Flora SJ. Defence Institute of
Physiology and Allied Sciences, Timarpur, Delhi, India.
Biomed Environ Sci 1998 Mar;11(1):7-14
Effect of vitamin C supplementation in restoring lead
induced alterations in hematopoietic system and drug
metabolizing enzymes were investigated in male rats.
Intraperitoneal administration of 20 mg/kg lead produced a
significant inhibition of heme synthesis in blood and liver
and drug metabolism in liver. Toxic insult by lead also
resulted into a marked decline in tissue thiols and vitamin
C levels. Oral supplementation of vitamin C (100 mg/kg for
3 days) completely restored blood delta aminolevulinic acid
dehydratase, uroporphyrinogen I synthetase and a few drug
metabolizing enzymes. Level of vitamin C and sulfhydryl
contents too recovered to a great extent. A marked
reduction in blood and liver lead concentration occurred on
vitamin C supplementation although renal lead contents were
marginally reduced in lead exposed animals. The results,
thus, indicate a significant protective action of vitamin C
against toxic effects of lead on heme synthesis and drug
metabolism.
Vitamin A
supplementation: implications for morbidity and mortality
in children.
Villamor E, Fawzi WW. Departments of Nutrition and
Epidemiology, Harvard School of Public Health, Boston, MA
02115, U.S.A. J Infect Dis 2000 Sep;182 Suppl 1:S122-33
Vitamin A deficiency impairs epithelial integrity and
systemic immunity and increases the incidence and severity
of infections during childhood. However, findings from
vitamin A supplementation trials are not consistent.
Supplementation has resulted in significant reductions in
mortality in several (but not all) large community-based
trials among apparently healthy children. In hospital-based
studies, vitamin A supplements have been consistently found
to reduce the severity of measles infection, but no effect
on nonmeasles respiratory infections has been observed. In
some cases, the supplements were associated with an
apparently increased risk of lower respiratory infection.
Vitamin A supplements also reduced the severity of diarrhea
in most (but not all) trials. Potential explanations for
the differences in efficacy across trials are reviewed.
While vitamin A supplementation is effective in reducing
total mortality and complications from measles infections,
it is likely to be more effective in populations suffering
from nutritional deficiencies.
Maternal-fetal
distribution of mercury (203Hg) released from dental
amalgam fillings.
Vimy MJ, Takahashi Y, Lorscheider FL. Department of
Medicine, Faculty of Medicine, University of Calgary,
Alberta, Canada. Am J Physiol 1990 Apr;258(4 Pt
2):R939-45
In humans, the continuous release of Hg vapor from
dental amalgam tooth restorations is markedly increased for
prolonged periods after chewing. The present study
establishes a time-course distribution for amalgam Hg in
body tissues of adult and fetal sheep. Under general
anesthesia, five pregnant ewes had twelve occlusal amalgam
fillings containing radioactive 203Hg placed in teeth at
112 days gestation. Blood, amniotic fluid, feces, and urine
specimens were collected at 1- to 3-day intervals for 16
days. From days 16-140 after amalgam placement (16-41 days
for fetal lambs), tissue specimens were analyzed for
radioactivity, and total Hg concentrations were calculated.
Results demonstrate that Hg from dental amalgam will appear
in maternal and fetal blood and amniotic fluid within 2
days after placement of amalgam tooth restorations.
Excretion of some of this Hg will also commence within 2
days. All tissues examined displayed Hg accumulation.
Highest concentrations of Hg from amalgam in the adult
occurred in kidney and liver, whereas in the fetus the
highest amalgam Hg concentrations appeared in liver and
pituitary gland. The placenta progressively concentrated Hg
as gestation advanced to term, and milk concentration of
amalgam Hg postpartum provides a potential source of Hg
exposure to the newborn. It is concluded that accumulation
of amalgam Hg progresses in maternal and fetal tissues to a
steady state with advancing gestation and is maintained.
Dental amalgam usage as a tooth restorative material in
pregnant women and children should be reconsidered.
Silymarin: a review of
its clinical properties in the management of hepatic
disorders.
Wellington K, Jarvis B. Adis International Limited,
Auckland, New Zealand. demail@adis.co.nz BioDrugs
2001;15(7):465-89
The mechanisms of action of silymarin involve different
biochemical events, such as the stimulation of the
synthetic rate of ribosomal RNA (rRNA) species through
stimulation of polymerase I and rRNA transcription,
protecting the cell membrane from radical-induced damage
and blockage of the uptake of toxins such as
alpha-amanitin. Studies in patients with liver disease have
shown that silymarin increases superoxide dismutase (SOD)
activity of lymphocytes and erythrocytes, as well as the
expression of SOD in lymphocytes. Silymarin has also been
shown to increase patient serum levels of glutathione and
glutathione peroxidase. Silybin 20 to 48 mg/kg/day has
shown promise as a clinical antidote to acute Amanita
(deathcap mushroom) poisoning. Primary efficacy data from 3
trials which examined the therapeutic potential of
silymarin in patients with cirrhosis, and included patient
survival as an end-point, demonstrated that silymarin had
no significant beneficial effect on patient mortality.
However, upon subanalysis, silymarin 420 mg/day had a
significantly beneficial effect on patient survival rate
(compared with patients receiving placebo) in 1 randomised,
double-blind trial in patients with alcoholic cirrhosis.
Silymarin 420 mg/day was also shown to improve indices of
liver function [AST, ALT, gamma-glutamyl transferase and
bilirubin] in patients with liver disease of various
aetiology, including those exposed to toxic levels of
toluene or xylene; however, it was largely ineffective in
patients with viral hepatitis. Reports of adverse events
while receiving silymarin therapy are rare. However, there
have been accounts of nausea, epigastric discomfort,
arthralgia, pruritus, headache and urticaria. Silymarin has
also been reported to have possibly caused a mild laxative
effect. CONCLUSION: The antioxidant properties of silymarin
(a mixture of at least 4 closely related flavonolignans, 60
to 70% of which is a mixture of 2 diastereomers of silybin)
have been demonstrated in vitro and in animal and human
studies. However, studies evaluating relevant health
outcomes associated with these properties are lacking.
Although silymarin has low oral absorption, oral dosages of
420 mg/day have shown some therapeutic potential, with good
tolerability, in the treatment of alcoholic cirrhosis.
Moreover, silybin 20 to 48 mg/kg/day has shown promise as
an antidote for acute mushroom poisoning by Amanita
phalloides; however, further studies paying attention to
the amount of ingested mushroom and time elapsed before
administration of treatment are needed to clarify its role
in this indication. Studies in patients with the early
onset of liver disease may demonstrate the liver
regeneration properties that silymarin is promoted as
possessing.
Chelation therapy:
conventional treatments.
Wentz PW. (LabCorp., Burlington, NC). May 2000 Advance
Magazines for Administrators of the Laboratory
(http://www.advanceforal.com/common/editorial/editorial/aspx).
Merion Publications, King of Prussia, PA
Maternal low level lead
and pregnancy outcomes.
West WL, Knight EM, Edwards CH, Manning M, Spurlock B,
James H, Johnson AA, Oyemade UJ, Cole OJ, Westney OE, et
al. Department of Pharmacology, College of Medicine, Howard
University, Washington, D.C. 20059.
J Nutr 1994 Jun;124(6 Suppl):981S-986S
We examined the relationship between the concentrations
of blood lead and pregnancy outcomes in a subset of 349
African American women who enrolled in the program project,
"Nutrition, Other Factors, and the Outcome of Pregnancy."
Vitamin-mineral supplement users had significantly higher
serum levels of ascorbic acid and vitamin E. Also, in
supplement users, there were significantly lower mean
concentrations of maternal blood lead. Inverse correlations
were found between maternal levels of lead and the
antioxidant vitamins, vitamin E and ascorbic acid. In
addition, significant Pearson's correlations were observed
between maternal blood lead levels and the following
variables: positive correlations with calcium, phosphorus,
mean corpuscular volume; inverse correlations with
gestational age, Ponderal Index, infant orientation, and
hematologic values. In the total subset, the three
trimester sample means for maternal blood lead
concentrations were not significantly different for mothers
of infants who weighed less than 2500 g (low birth weight)
and those who were delivered infants who weighed 2500 g or
more. Clinically, nutrition may play a role in the
reduction of potentially adverse effects from lead during
pregnancy, i.e. protection of the fetus against lead
toxicity and/or free radical damage through the antioxidant
actions of vitamin E and ascorbic acid. Even when maternal
blood lead levels are within the so-called "safe" range,
maternal/use of a vitamin supplement supplying vitamin E
and ascorbic acid during pregnancy may offer
protection.
Aluminum.
WHO (no authors given). 1998 Guidelines for
Drinking-Water Quality, Second Edition, Health Criteria and
Other Supporting Information, pp. 3-13
(http://www.who.into/water_sanitation_health/GDWQ/Chemicals/aluminfull.html).
World Health Organization, Geneva.
No health-based guideline value for aluminium was
recommended in the second edition of the WHO Guidelines for
drinking-water quality. It was concluded that although
further studies were needed, the balance of epidemiological
and physiological evidence did not support a causal role
for aluminium in Alzheimer disease. An aluminium
concentration of 0.2 mg/litre in drinking-water provided a
compromise between the practical use of aluminium salts in
water treatment and discoloration of distributed water. The
Coordinating Committee for the updating of the WHO
Guidelines recommended that a health criteria document be
prepared for aluminium, based on the IPCS Environmental
Health Criteria monograph that was finalized in 1995.
[Mercury concentration
in the mouth mucosa of patients with amalgam
fillings.] [Article in German]
Willershausen-Zonnchen B, Zimmermann M, Defregger A,
Schramel P, Hamm G. Poliklinik fur Zahnerhaltung und
Parodontologie, Universitat Munchen. Dtsch Med Wochenschr
1992 Nov 13;117(46):1743-7
Mercury concentrations were measured in specimens of
oral mucosa taken during oral surgery from 90 patients (53
men, 37 women, mean age 42 +/- 16 years); 30 of the
patients had no amalgam fillings. All the mucosal specimens
extended for at least 2-3 mm from the epithelium of the
gingival margin and were clinically and radiologically
normal. Thirteen patients without metallic fillings of any
kind had mercury concentrations of 118.4 +/- 83.7 ng/g
tissue, and in 17 patients with precious metal fillings but
no amalgam the mean mercury concentrations were 144 +/- 290
ng/g tissue. Seventeen patients with 1-3 amalgam fillings
had an average of 1975 +/- 4300 ng/g tissue and in 26
patients with 3-6 amalgam fillings the average
concentration was 1158 +/- 2500 ng/g tissue. In 17 patients
with more than six amalgam fillings the mean mercury
concentration was 2302 +/- 5600 ng/g tissue. Although these
results demonstrate a considerable degree of transfer of
mercury from the amalgam fillings to the oral mucosa, it
had not resulted in any clinically detectable mucosal
lesions.
Effects of lead on
glutathione S-transferase expression in rat kidney: a
dose-response study.
Wright LS, Kornguth SE, Oberley TD, Siegel FL. Waisman
Center, University of Wisconsin, Madison, WI 53705, U.S.A.
Toxicol Sci 1998 Dec;46(2):254-9
Glutathione S-transferases (GST, EC 2.5.1.18) are a
family of phase II detoxification enzymes involved in the
conjugation of glutathione to a highly diverse group of
compounds. The purpose of this study was to evaluate the
dose-response effects of lead acetate administration on the
expression of rat kidney GST. Sprague-Dawley rats were
injected with doses of lead acetate ranging from 0.11 to
114 mg/kg (0.3 to 300 mumol/kg) for three consecutive days
and sacrificed 24 h later. Kidney GST activity, GST isoform
HPLC profiles, blood lead analysis, and electron microscopy
were performed. A dose of 1.1 mg/kg lead acetate resulted
in a blood lead level of 26 micrograms/dl and produced a
significant increase in GST activity which continued to
increase with dose up to 38 mg/kg. Morphological changes
were detected at 3.8 mg/kg and increasing severity of
cellular damage paralleled dose, blood lead levels, and
changes in body weight. Individual GST isoforms exhibited
different thresholds and maxima; rGSTP1 and rGSTM1 had
thresholds of 1.1 and 3.8 mg/kg, respectively, very similar
rates of increase with dose, and a maximum yield that was
450% above control at a dose of 38 mg/kg for both enzymes.
rGSTA1 and rGSTA3 showed similar thresholds (1.1 mg/kg) and
maximal fold increase (275%) but varied in the relative
response to each dose. These results indicate that renal
GST increases occur at lead levels which are
environmentally significant, that these changes precede
cellular damage, and suggest that GST may serve as a tissue
biomarker of lead exposure.
Metabolic methylation
is a possible genotoxicity-enhancing process of inorganic
arsenics.
Yamanaka K, Hayashi H, Tachikawa M, Kato K, Hasegawa A,
Oku N, Okada S. Department of Biochemical Toxicology, Nihon
University College of Pharmacy, Chiba, Japan. Mutat Res
1997 Nov 27;394(1-3):95-101
To elucidate if the metabolic methylation participates
in the induction of inorganic arsenic-responsible genetic
damage, arsenite (ARS) and its methylated metabolites,
methanearsonic acid (MMAA) and dimethylarsinic acid (DMAA),
were comparatively assayed for the induction of DNA damage
by determining DNA repair synthesis using polymerization
inhibitors such as aphidicolin (aph) and hydroxyurea (HU).
When human alveolar epithelial type II (L-132) cells in
culture were exposed to either one of these three arsenic
compounds, DNA single-strand breaks resulting from the
inhibition of repair polymerization were remarkably
produced by exposure to DMAA at 5 to 100 microM, while not
by that to ARS and MMAA even at 100 microM. Furthermore, a
bromodeoxyuridine (BrdrU)-photolysis assay indicated that
the induction of DNA repair synthesis was observed only in
the case of exposure to DMAA. When L-132 cells were exposed
to 100 microM MMAA in the presence of 10 mM
S-adenosyl-L-methionine (SAM), which is a well-known
methyl-group donor in metabolic methylation of arsenics,
DNA repair synthesis was induced along with an increase in
the amount of dimethylarsenic in the cells. These results
indicate that metabolic methylation of inorganic arsenics
to dimethylarsenics is predominantly involved in the
induction of DNA damage.
Mercury use in
espiritismo: a survey of botanicas.
Zayas LH, Ozuah PO. Am J Public Health 1996
Jan;86(1):111-2
No abstract available.
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