Note: The following is a limited selection of abstracts
from 1994 to present.
Due to length, we present this as a separate section
• Click here to return to the 4-part Blood
for fluorine & organofluorine pesticides.
When time allows more information will be added.
& Bone Damage: Published Data.
• TABLE 3a:
Average Serum Fluoride Levels Reported
in Human Skeletal Fluorosis
• TABLE 3b:
Serum Fluoride Levels Causing Damage
to Mineralized Tissues in Rats
• TABLE 3c:
Maximum Serum Fluoride Levels in
Humans Living in < 1.9 ppm areas
• TABLE 7:
The Relationship of Water Fluoride
to Serum Fluoride in Rats
Compiled by Michael Connett.
Submission to the National Research Council Committee
"Subcommittee on the Toxicologic Risk of Fluoride
in Drinking Water; BEST-K-02-05-A".
January 29, 2004.
for this submission
sodium fluoride on total
serum protein levels and transaminase
activity in rats.
D, Laghaie B, Gholipour A, Solimani N, Hassenzadeh S.
Department of Biochemistry and Biophysics, Babol University of Medical
Sciences, Iran. email@example.com
Transaminase activity and serum total protein level were investigated
in adult rats after oral treating with sodium
fluoride at three doses, 10, 20 and 30 mg/kg daily for 90
days. After 90 days, the average total serum
protein level of the rats in the treatment group decreased significantly
compared with that in the control [1.9 +/- 0.1 (mean +/-
S.D., n = 140) vs. 3.1 +/- 0.2] mg/dl, P< 0.05. Serum transaminase
activity in the treatment group increased compared with that in
the control [5.3 +/- 0.4 (mean +/- S.D., n = 140) vs. 3.2 +/- 0.3]
micromol/min per ml, P < 0.05.
PMID: 12109808 [PubMed - in process]
fluoride intoxication on lipid peroxidation and antitoxidant systems
(a), AR Shivashankara (a), P Gopalakrishna Bhat (b), S Hanumanth
(a) YM Shivarajashankara,
Dept. of Biochemistry, MR Medical Col-lege, Gulbarga-585 105, Karnataka,
India; E-mail: firstname.lastname@example.org;
(b) Dept. of Biochemistry, Kasturba Medical College, Manipal-576
119, Karnataka, India;
(c) Dept. of Biochemistry, KBN Institute of Medical Sciences, Gulbarga-585
104, Karnataka, India.
SUMMARY: The effect of
fluoride intoxication on lipid peroxidation and anti-oxidant systems
in the blood, brain, and liver of rats was studied. Twelve one-month-old
albino rats were administered 100-ppm fluoride (as NaF) in their
drinking water for four months. In the red blood cells the levels
of malondial-dehyde (MDA) and glutathione (GSH) increased, along
with the activity of glutathione peroxidase (GSH-Px), but the activity
of superoxide dismutase (SOD) decreased. In the plasma the level
of ascorbic acid increased while that of uric acid decreased. In
the brain and liver, MDA and GSH levels increased, as did the activities
of GSH-Px and glutathione S-transferase (GST). The level of ascorbic
acid increased in the brain, but it decreased in the liver.
These results suggest that fluoride enhances lipid peroxidation
in the red blood cells, brain and liver of rats and causes increased
or decreased enzyme activity associated with free radical metabolism.
metabolism in rats exposed to high-fluoride water and effect of
Kaushik (a), Radhey Shyam (b), Praveen Vats (b), Shoba Suri (b),
MML Kumria (b), PC Sharma (a), Som Nath Singh (b)
(a) Dept. of Biotechnology,
Chaudhary Charan Singh University, Meerut-250 004, India.
(b) For correspondence: Dr Som Nath Singh, Nutrition Division, Defence
Institute of Physiology and Allied Sciences, Timarpur, Delhi-110
054, India. Email: email@example.com
SUMMARY: Effects of high
fluoride intake through water on glutathione and related enzymatic
activities in blood and liver of albino rats were studied. Twenty
four rats were divided into three groups of 8 each. Group I was
given normal municipal supply water (fluoride content 0.55 ppm),
Groups II and
III were exposed
to 12 ppm fluoride in water for 15 days. Group III was treated orally
with Spirulina ¨ (200 mg/kg bwt), a functional food rich in protein,
vitamins and minerals, for study of protective effects. After 15
days of exposure reduced and oxidised glutathione (GSH and GSSG),
lipid peroxidation and enzymes, i.e. glutathione reductase (GR),
glutathione peroxidase (GPx), gluta-thione S-transferase (GST),
and y-glutamyl transpeptidase (y-GT) activities were measured in
blood/erythrocytes and liver. There was a
significant rise in blood GSSG level and a decrease in GSH/GSSG
ratio, with increased lipid peroxidation in fluoride-exposed animals.
A marked decrease in GR and GST activities and an increase in y-glutamyl
transpeptidase activity were also noted in blood of fluoride exposed
animals. In the liver no significant changes in these variables
were observed. Results indicate oxidative
stress during fluoride exposure. Spirulina treatment was
beneficial to some extent as a rich source of the antioxidant vitamin
Int J Occup Med Environ
of sodium fluoride on the adenine nucleotide
pool in erythrocytes of Wistar rats.
Department of Biochemistry, Institute of Life Sciences, University
of Szczecin, Poland. firstname.lastname@example.org
The effect of sodium fluoride on the
content of adenine nucleotides, adenine nucleotide pool and energy
potential of erythrocytes was studied in male Wistar rats, depending
on the dose and time of exposure. Sodium fluoride
was administered for 4 and 8 weeks at 4 or 16 ppm through a gastric
tube. The concentration of fluorine in serum, ATP, ADP and AMP content
in blood and erythrocytes, adenine nucleotide pool and energy potential
of erythrocytes were calculated. The results were expressed in SI
units and compared statistically with Student's t-test (Statgraphics
v. 5.0 software). A significant reduction
in the content of ATP and ADP and an increase in the content of
AMP in erythrocytes was found after
4 weeks of exposure to 4 or 16 ppm NaF.
The adenine nucleotide pool and
energy potential were reduced with the smaller dose. After 8 weeks,
the ADP content remained significantly
reduced with the smaller dose, while the greater dose was associated
with a higher energy potential of the cells. Correlations between
serum concentration of fluorine, content of adenine nucleotides
and adenine nucleotide pool in erythrocytes were noted in all study
PMID: 11885920 [PubMed - indexed for MEDLINE]
of fluoride ions on Na+-H+ exchanger actvity in human red
(a,b), D Chlubek (a), E Kwiatkowska (c), K K ¥ dziersk (c), E Stachowska
(a), P Wieczorek (a) E Byra (d), Z Machoy (a), E Herdzik (c)
(a) Department of Biochemistry
and Chemistry. Pomeranian Academy of Medicine (PAM).
(b) For correspondence: Dept. of Biochem. and Chem., PAM, 70- 111
Szczecin, Al. Pow-stancow Wlkp.72, Poland.; E-mail: email@example.com,
(c) Chair and Dept. of In-ternal Medicine,
(d) Main Laboratory, Clinical Hospital of PAM.
Summary: The influence
of fluoride ion (F - ) at concentrations
of 0.25 and 2.5 mM on intracellular pH and Na + -H + exchanger (NHE)
activity in human red blood cells was investigated. Erythrocytes
from 15 healthy individuals were examined. We
found that F - caused a decrease in NHE activity and an increase
in intracellular H + ion concentration (decrease of intracellular
pH). marrow haematopoietic cells.
Am J Physiol Lung Cell
Mol Physiol 2001 Dec;281(6):L1472-83
Mechanisms of sodium fluoride-induced
endothelial cell barrier dysfunction:
role of MLC phosphorylation.
P, Verin AD, Birukova A, Gilbert-McClain LI, Jacobs K, Garcia JG.
Division of Pulmonary and Critical Care Medicine, Johns Hopkins
University School of Medicine, Baltimore, Maryland 21224-6801, USA.
NaF, a potent
G protein activator and Ser/Thr phosphatase inhibitor, significantly
increased albumin permeability and decreased transcellular
electrical resistance (TER), indicating endothelial cell (EC) barrier
barrier dysfunction induced by NaF
was accompanied by the development of actin stress fibers, intercellular
gap formation, and significant time-dependent
increases in myosin light chain (MLC) phosphorylation. However,
despite rapid, albeit transient, activation of Ca(2+)/calmodulin-dependent
MLC kinase (MLCK), the specific MLCK inhibitor ML-7 failed to affect
NaF-induced MLC phosphorylation, actin
cytoskeletal rearrangement, and reductions in TER, suggesting a
limited role of MLCK in NaF-induced
EC activation. In contrast, strategies to reduce Rho (C3 exoenzyme
or toxin B) or to inhibit Rho-associated kinase (Y-27632 or dominant/negative
RhoK) dramatically reduced MLC phosphorylation and actin stress
fiber formation and significantly attenuated
NaF-induced EC barrier dysfunction.
Consistent with this role for RhoK activity, NaF
selectively inhibited myosin-specific phosphatase activity, whereas
the total Ser/Thr phosphatase activity remained unchanged. These
data strongly suggest that MLC phosphorylation, mediated primarily
by RhoK, and not MLCK, participates in NaF-induced
EC actin cytoskeletal changes and barrier dysfunction.
PMID: 11704544 [PubMed - indexed for MEDLINE]
Adv Exp Med Biol 2001;498:263-71
in g-protein-linked signal transduction
in vascular smooth muscle in diabetes.
MB, Wang R, Liu YY.
Department of Physiology, Faculty of Medicine, University of Montreal,
The present studies
were undertaken to determine the levels of stimulatory and inhibitory
guanine nucleotide regulatory proteins (Gs and Gi respectively)
and their relationship with adenylyl cyclase activity in aorta from
5-day streptozotocin-induced diabetic (STZ) rats. The levels of
Gi alpha-2 as determined by immunoblotting techniques using AS/7
antibody were significantly decreased by about 60% in STZ as compared
to control rats, whereas the levels of Gs alpha were not altered.
In addition, the stimulatory effect of cholera toxin (CT) on GTP-sensitive
adenylyl cyclase was not different in STZ as compared to control
rats. On the other hand, the stimulatory effects of GTPgammaS, isoproterenol,
glucagon, forskolin (FSK) and sodium fluoride
on adenylyl cyclase were enhanced in STZ-rats. Furthermore, GTPgammaS
inhibited FSK-stimulated adenylyl cyclase activity in a concentration-dependent
manner (receptor independent functions of Gi) in control rats which
was almost completely abolished in STZ rats. In addition, receptor-mediated
inhibition of adenylyl cyclase by angiotensin II (AII), oxotremorine
and atrial natriuretic peptide (ANP) was attenuated in STZ rats.
These results suggest that the decreased expression of Gi alpha,
but not of Gs alpha, may be responsible for the observed altered
responsiveness of adenylyl cyclase to hormonal stimulation and inhibition
in STZ-rats. It may thus be suggested that
the decreased Gi activity may be one of the possible mechanisms
responsible for the impaired vascular functions in diabetes.
11900377 [PubMed - indexed for MEDLINE]
report available at: http://www.fluoride-journal.com/00-33-3/333-108.pdf
of fluoride ions on the viability, reduction of NBT, cytolysis,
degranulation, and phagocytosis of human and
(,a,b), E Kucharsk (c), J Zawierta (a), Z Machoy (a), D Chlubek
(a), K Ciechanowski (a)
Chair and Department of Biochemistry, Pomeranian Academy of Medicine,
Al. Powsta ców Wlkp. 72, 70-111 Szczecin, Poland.
E-mail: firstname.lastname@example.org (Head: Asst Prof Dariusz Chlubek,
(b) For correspondence: Joanna Bober, MD, PhD, same address.
(c) Chair and Department of Microbiology and Immunology, Pomeranian
Academy of Medicine, Al. Powsta ców Wlkp. 72, 70-111
The influence of fluoride ion at concentrations of 10, 20, and 30
mmol/L on various properties of human and rabbit granulocytes was
investigated. We found that fluoride ion inhibited phagocytes functions
of rabbit granulocytes. It also decreased the viability of rabbit
polymorphonuclear leukocytes (PMN) which was connected with increased
degranulation. Fluoride ion activated mainly the oxygen-dependent
bactericidal system in human neutrophils and the oxygen-independent
one in rabbit neutrophils.
influence of sodium fluoride on the clonogenicity of human
hematopoietic progenitor cells:
Machaliski (a), Maria Zejmo, Iwona Stecewicz, Anna Machalinska,
Zygmunt Machoy, Mariusz Z Ratajczak
(a) For Correspondence:
Department of General Pathology, Pomeranian Academy of Medicine,
Al. Powstaców Wlkp. 72, 70-111 Szczecin, Poland. E-mail:
SUMMARY: Since fluoride
accumulates not only in bones but also in bone marrow cavities where
hematopoiesis occurs, a preliminary study was under-taken of the
potential toxicity of sodium fluoride (NaF)
against early human myeloid (CFU-GM, Colony Forming Unit of Granulocyte-Macrophages)
and erythroid (BFU-E, Burst Forming Unit of Erythrocytes) progenitors.
CD34 + cells isolated from human umbilical cord blood were exposed
for 30 and 120 min at 37 o C or 4 o C to increasing concentrations
of NaF (0, 1, 10 and 50 mM). At 1 mM
NaF, a detectable but not statistically
significant stimulatory effect was observed in 7 of the 8 different
sets of experiments. At 10 and 50 mM, however,
NaF was significantly toxic against cord blood CFU-GM and BFU-E
progenitors. Fluoride may therefore be potentially toxic toward
early human hematopoietic cells.