Antithyroid effect of a food or drug preservative: 4-hydroxybenzoic acid methyl ester

Abstract

Summary. 4-hydroxybenzoic acid methyl ester (methylparaben) inhibits organification of iodide by isolated hog thyroid cells. The concentration which produces a 50% inhibition was about 2.0 x 10-4M. A similar inhibition was observed in nonstimulated and TSH-or dibutyryl cyclic AMP-stimulated cells. Neither iodide uptake nor cyclic AMP generation were altered by methylparaben.Antithyroid drugs refer to a group of compounds that block the synthesis of thyroid hormones. These compounds fall into 2 main categories: a) compounds that inhibit accumulation of iodide by the thyroid gland, b) compounds that interfere with the utilization of iodide into the gland. The compounds of the 2nd group exert their inhibitory effect by blocking one or several of the following reactions: oxydation of iodide, formation of iodotyrosines, coupling of iodotyrosines to form thyroid hormones. Besides, thionamides which are the most potent antithyroid agents, phenol and benzoic acid derivatives (resorcinol, p-aminobenzoic acid ...) are known to be efficient inhibitors of iodine metabolism both in vivo and in vitro. During the course of our study on the metabolism of iodide in dispersed thyroid cells, we found that 4-hydroxybenzoic acid methyl ester, a compound used as a food or drug preservative, prevented thyroid hormone synthesis. In this communication we report that this compound inhibits the organification of iodide without altering the iodide trapping mechanism. Suspensions of dispersed hog thyroid cells were prepared as previously described I. Thyroid cells (1 5 • 107) were incubated in Earle's balanced salt solution, pH 7.4, in the presence of 0.05/~M iodide labelled with 1-5/~Ci 131I, for 2 h at 37 ~ with air as the gas phase and under constant shaking (60 cycles/rain). Iodide trapping, expressed in terms of 1311-C/M ratio: the ratio between intracellular and medium labelled iodide concentration, was determined in the presence of 2 mM methimazole according to Rodesch and Dumont:. Iodide organification was assessed by measurements of 13q-iodide incorporation into acid-insoluble material (mainly iodoproteins). Cell homogenates were supplemented with 0.1 ml 0.2 mM NaI and 0.1 ml 1% (w/v) bovine serum albumin and proteins were precipitated with 5~ (w/v) trichloracetic acid. The 1500• g pellet was washed with 5% trichloracetic acid and counted for radioactivity. Cyclic AMP was assayed as previously described 3. Thyrotropin (TSH),N6,O2'-dibutyryl-adenosine 3':5' monophosphate (db cAMP) and 4-hydroxybenzoic acid methyl ester were obtained from Armour (Kankakee, USA), Sigma (St. Louis, USA) and Organon (France), respectively.

Phenols and parabens in relation to reproductive and thyroid hormones in pregnant women

“…However, iodine may act as a mechanistic intermediate between exposure and thyroid disruption (Koeppe et al, 2013; Rousset, 1981), and controlling for iodine status could lead to further bias.…”

Environmental chemicals and thyroid function

“…Recent studies suggest that parabens possess estrogenic potential, but no studies have focused on thyroid toxicity (90). Methylparaben seemed to have a weak intrinsic antithyroid activity in vitro by dose-dependently inhibiting iodide organification (91).…”

Relationship between urinary triclosan and paraben concentrations and serum thyroid measures in NHANES 2007–2008

“…While a number of in vitro studies have suggested mechanisms by which these chemicals may exert thyroid disrupting effects (Jinno et al, 1997; Rousset, 1981; Schuur et al, 1998; Taxvig et al, 2008; Wang et al, 2004), direct impacts of triclosan and paraben exposures on TH levels have only recently been investigated in rat models. These studies have demonstrated the ability of triclosan and parabens to decrease TH levels in vivo (Crofton et al, 2007; Paul et al, 2010; Vo et al, 2010; Zorrilla et al, 2009).…”