Thyroid peroxidase activity as toxicity target for fluoride in patients with thyroid dysfunction
https://www.google.com/search?q=flou...icial&start=20 (free full paper PDF)
Swati Singla and Shashi A*
Department of Zoology, Punjabi University, Patiala- 147002, Punjab, India
* Corresponding author: Shashi Aggarwal, email:
shashiuniindia@yahoo.co.in
ABSTRACT
The present study aimed to assess the effects of drinking water fluoride (F) on the activity of thyroid peroxidase (TPO) enzyme involved in thyroid hormone synthesis. 840 fluorotic patients affected with thyroid hypo and
hyper function and 140 euthyroid without fluorosis representing control were randomly selected from high endemic fluoride areas of Bathinda district, Punjab, India. The findings indicate significant (P<0.001) increase in the levels of serum F, urinary F and Urinary iodine (I) in fluorotic patients affected with thyroid disease.
Significant (P<0.001) inhibition was recorded in activity of TPO in fluorotic patients with thyroid hypofunction and the activity was elevated in hyperthyroid fluorotic patients. Pearson’s bivariate correlation revealed strong positive correlation between water F and serum F (r= 0.98, P<0.01). Negative correlation existed between serum F vs TPO (r= -0.93, P<0.003), urinary I vs TPO (r = -0.95, P<0.002) and serum TSH vs TPO (r = -0.8876, P<0.001). The activity of TPO showed positive correlation with T3 (r = 0.963, P<0.01) as well as with T4 (r = 0.965, P<0.001).
From the present study it may be concluded that the ingestion of drinking water with high concentration of fluoride leads to stress of the mechanism of biosynthesis of thyroid hormones, as evidenced by depletion in the activity of TPO, which may be produced by the attraction of fluoride with oxidized form of iodide and/or with the iodide site on the TPO molecule. This tends to decrease in concentration of T3, T4 and increase production of TSH in the serum.
INTRODUCTION
Over the past decade there has been an increasing focus
on the effects of hazardous chemicals on human
endocrine systems. Exposure to specific environmental
toxins has been shown to interfere with the production,
transportation and metabolism of thyroid hormones
(TH) by a variety of mechanisms or in modifying the
metabolism of thyroid hormones. Environmental
endocrine disruptors are exogenous substances that
can interfere with TH synthesis, deiodinase function in
peripheral tissues, proteins in the blood, and the
agonistic or antagonistic actions of certain chemicals on
target tissue receptors [1].
Fluorine containing
compound have been listed among the most significant
endotoxins that appear in natural environment as after
effects of industrial activity of humans. The high cell
membrane penetrating power, bioaccumulation, and
biodegradable property of fluoride cause it to have a
major impact on ecotoxicology [2].
The U.S National Research Council [3] states fluoride is
an endocrine disruptor and has the potential to disrupt
the function of many tissues that require iodine. Studies
that have examined human populations with adequate
intake of iodine have reported mixed results about
fluoride’s ability to produce goiter [4]. The research has
been more consistent, however, where the examined
populations had either excessive iodine intakes [5], or
deficient iodine intakes [6]. Thyroid disruptors can
affect thyroid physiology in many phases of thyroid
regulation. The complex system of iodine uptake,
thyroid hormone production, interconversion of
thyroid hormones and hormone degradation and
elimination can be directly altered by thyroid
disruptors [7].
And in the body of the text
Fluoride had significant effect on TPO activity, and
decreases T3 and T4 levels and increases TSH. This
disruption of TPO activity could be a sensitive TH end
point for various concentrations of water fluoride.
Several chlorinated POPs disrupt the TH axis, including
polychlorinated biphenyls, polychlorinated dibenzo-pdioxins,
and dibenzofurans [25,26]. In animal studies,
Boas et al. [27] reported that fluorinated compounds
such as PFOS and PFOA also inhibited TPO activity in
the rats, with reductions in T4 and T3.
PFOS
http://en.wikipedia.org/wiki/Perfluo...esulfonic_acid
PFOA
http://en.wikipedia.org/wiki/Perfluorooctanoic_acid
and there is a great table showing urine and serum fluorine levels for various intakes of fluorine ; they rise "significantly" as does iodine excretion !
The increase level of urinary iodine with increasing fluoride intake is striking. They do not record the iodine intakes, but this raises some interesting questions as to why more iodine is being excreted in those with a high fluoride intake - if intakes of iodine are already low would this be a double high fluoride intake whammy?
Should all thyroid function assessments also look at flouride levels ? I have no idea to what extent the issue is on the wider public health adgenda. This is the NHS UK information of fluoride that I found http://www.nhs.uk/Conditions/Fluorid...roduction.aspx makes no mention of flouride and potential impact on thyroid function on this page.