Phthalates Induce Neurotoxicity Affecting Locomotor and Thermotactic Behaviors and AFD Neurons through Oxidative Stress in Caenorhabditis elegans

I-Ling Tseng,Ying-Fei Yang,Wen-Hsuan Li,Chan-Wei Yu,Vivian Hsiu-Chuan Liao,Michael Hendricks

doi:10.1371/journal.pone.0082657

Abstract

BackgroundPhthalate esters are ubiquitous environmental contaminants and numerous organisms are thus exposed to various levels of phthalates in their natural habitat. Considering the critical, but limited, research on human neurobehavioral outcomes in association with phthalates exposure, we used the nematode Caenorhabditis elegans as an in vivo model to evaluate phthalates-induced neurotoxicity and the possible associated mechanisms.Principal FindingsExposure to phthalates (DEHP, DBP, and DIBP) at the examined concentrations induced behavioral defects, including changes in body bending, head thrashing, reversal frequency, and thermotaxis in C. elegans. Moreover, phthalates (DEHP, DBP, and DIBP) exposure caused toxicity, affecting the relative sizes of cell body fluorescent puncta, and relative intensities of cell bodies in AFD neurons. The mRNA levels of the majority of the genes (TTX-1, TAX-2, TAX-4, and CEH-14) that are required for the differentiation and function of AFD neurons were decreased upon DEHP exposure. Furthermore, phthalates (DEHP, DBP, and DIBP) exposure at the examined concentrations produced elevated intracellular reactive oxygen species (ROS) in C. elegans. Finally, pretreatment with the antioxidant ascorbic acid significantly lowered the intracellular ROS level, ameliorated the locomotor and thermotactic behavior defects, and protected the damage of AFD neurons by DEHP exposure.ConclusionsOur study suggests that oxidative stress plays a critical role in the phthalate esters-induced neurotoxic effects in C. elegans.

Highlights

Endocrine-disrupting chemicals (EDC) are exogenous compounds that have the potential to alter hormonal and homeostatic systems, thereby affecting health and reproduction in animals and humans [1,2,3,4]
Our study suggests that oxidative stress plays a critical role in the phthalate esters-induced neurotoxic effects in C. elegans
We examined neurotoxicity induced by phthalates DEHP, dibutyl phthalate (DBP), and diisobutyl phthalate (DIBP), and the possible associated mechanisms in C. elegans

Summary

Introduction

Endocrine-disrupting chemicals (EDC) are exogenous compounds that have the potential to alter hormonal and homeostatic systems, thereby affecting health and reproduction in animals and humans [1,2,3,4]. Phthalates were postulated to produce endocrine-disrupting effects in rodents; animal research strongly implicated high-dose exposure to certain phthalates (DEHP, DBP, and BBP) altered developmental and reproductive functions in rats [12]. The observed adverse effects in rodent models raise concerns about whether phthalate exposure poses a potential health risk to humans. Phthalate esters are ubiquitous environmental contaminants and numerous organisms are exposed to various levels of phthalates in their natural habitat. Considering the critical, but limited, research on human neurobehavioral outcomes in association with phthalates exposure, we used the nematode Caenorhabditis elegans as an in vivo model to evaluate phthalates-induced neurotoxicity and the possible associated mechanisms

Objectives

Methods

Results

Conclusion