Quercetin Protects Human Thyroid Cells against Cadmium Toxicity.

Francesca Capriglione,Diego Russo,Valentina Maggisano,Jessica Maiuolo,Giuseppe Damante,Stefania Bulotta,Marilena Celano

doi:10.3390/ijms22136849

Francesca Capriglione, Diego Russo + Show 5 more

Open Access

https://doi.org/10.3390/ijms22136849

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Abstract

Various natural compounds have been successfully tested for preventing or counteracting the toxic effects of exposure to heavy metals. In this study, we analyzed the effects of cadmium chloride (CdCl2) on immortalized, non-tumorigenic thyroid cells Nthy-ori-3-1. We investigated the molecular mechanism underlying its toxic action as well as the potential protective effect of quercetin against CdCl2-induced damage. CdCl2 suppressed cell growth in a dose- and time-dependent manner (IC50 value ~10 μM) associated with a decrease in levels of phospho-ERK. In addition, CdCl2 elicited an increase in reactive oxygen species (ROS) production and lipid peroxidation. A significant increase in GRP78, an endoplasmic reticulum (ER) stress-related protein, was also observed. Supplementation of quercetin counteracted the growth-inhibiting action of CdCl2 by recovering ERK protein phosphorylation levels, attenuating ROS overproduction, decreasing MDA content and reducing the expression of GRP78 in cells exposed to CdCl2. Thus, in addition to revealing the molecular effects involved in cadmium-induced toxicity, the present study demonstrated, for the first time, a protective effect of quercetin against cadmium-induced damages to normal thyroid cells.

Highlights

In a study conducted by Uetani et al [6] in people living in a Cd-polluted area of Japan, Cd concentrations in the thyroid gland were three times higher compared to those residing in non-polluted areas [6]
Few studies have investigated the action of Cd on human thyroid cells and the underlying molecular and cellular mechanisms involved in thyroid toxicity, and most studies have been performed in cancer cell lines [7,8,9]
Since it has been reported that the flavone quercetin is able to prevent several damages caused by heavy metals, we tried to reverse the cytotoxic effect of CdCl2 by using this natural compound, dissolved in dimethyl sulfoxide (DMSO) at the concentration of 5 μM

Summary

Introduction

Cadmium (Cd) is one of the most toxic environmental pollutants derived from natural sources as well as human activities. The presence of cysteine-rich proteins containing thiol groups able to bind Cd makes even the thyroid gland a potential site of Cd deposition, and it has been reported that Cd blood concentration correlates positively with its accumulation in thyroid tissue [4,5]. In a study conducted by Uetani et al [6] in people living in a Cd-polluted area of Japan, Cd concentrations in the thyroid gland were three times higher compared to those residing in non-polluted areas [6]. Few studies have investigated the action of Cd on human thyroid cells and the underlying molecular and cellular mechanisms involved in thyroid toxicity, and most studies have been performed in cancer cell lines [7,8,9]

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