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Toxicology xxx (2012) xxxxxx
Toxicology
journal homepage: www.elsevier.com/locate/toxicol
Laboratory of Forensic Sciences and Toxicology, University of Crete, Voutes, 71003 Crete, Greece
University of Granada School of Medicine, Avda Madrid 11, 18071 Granada, Spain
Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland
a r t i c l e
i n f o
Article history:
Received 25 May 2012
Received in revised form
19 September 2012
Accepted 25 September 2012
Available online xxx
Keywords:
Glucose homeostasis
Lipid metabolism
Oxidative stress
Endocrine disrupting chemicals
Neurodevelopment
Neurodegeneration
a b s t r a c t
Organochlorine and organophosphate pesticides are compounds that can be detected in human populations as a result of occupational or residential exposure. Despite their occurrence in considerably
low levels in humans, their biological effects are hazardous since they interact with a plethora of
enzymes, proteins, receptors and transcription factors. In this review we summarize the cell and molecular effects of organochlorine and organophosphate pesticides with respect to their toxicity, with particular
emphasis on glucose and lipid metabolism, their interaction with some members of the nuclear receptor family of ligand-activated transcription factors, including the steroid and peroxisome proliferator
activated receptors that changes the expression of genes involved in lipid metabolism and xenobiotic detoxication. More importantly, evidence regarding the metabolic degradation of pesticides and
their accumulation in tissues is presented. Potential non-cholinergic mechanisms after long-term lowdose organophosphate exposure resulting in neurodevelopmental outcomes and neurodegeneration are
also addressed. We conclude that the mechanism of pesticide-mediated toxicity is a combination of
various enzyme-inhibitory, metabolic and transcriptional events acting at the cellular and molecular
level.
2012 Published by Elsevier Ireland Ltd.
1. Introduction
Pesticides constitute a diverse class of chemicals extensively
used for prevention of harmful effects caused by pests. Among
the large number of different pesticides those that are of particular concern are organophosphate (OPs) and organochlorines
(OCs). Despite their structural dissimilarities, these two classes
of pesticides result in neurological adverse effects through different mechanisms of toxicity. OPs mechanism of action involves
mainly inhibition of acetylcholinesterase (AChE) resulting in synaptic accumulation of acetylcholine and excessive stimulation of
cholinergic neurons. Nevertheless this mechanism cannot alone
account for some other effects such as neurodevelopmental alterations following low-dose chronic exposure by pregnant women. In
turn, OCs have afnity for the -subunit of the voltage-dependent
sodium channels in neurons, preventing their closing and resulting in repetitive ring of action potentials (Karami-Mohajeri and
Abdollahi, 2011). Primary adverse neurological effects of OC insecticides also result from inhibition of GABAA and glycine receptors
(Heusinkveld and Westerink, 2012).
Corresponding author. Tel.: +30 2810 394678; fax: +30 2810 542098.
E-mail address: aris@med.uoc.gr (A.M. Tsatsakis).
Please cite this article in press as: Androutsopoulos, V.P., et al., A mechanistic overview of health associated effects of low levels of organochlorine
and organophosphorous pesticides. Toxicology (2012), http://dx.doi.org/10.1016/j.tox.2012.09.011
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immediate detoxication of potentially harmful pesticide metabolites (Karami-Mohajeri and Abdollahi, 2011).
Please cite this article in press as: Androutsopoulos, V.P., et al., A mechanistic overview of health associated effects of low levels of organochlorine
and organophosphorous pesticides. Toxicology (2012), http://dx.doi.org/10.1016/j.tox.2012.09.011
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and organophosphorous pesticides. Toxicology (2012), http://dx.doi.org/10.1016/j.tox.2012.09.011
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Please cite this article in press as: Androutsopoulos, V.P., et al., A mechanistic overview of health associated effects of low levels of organochlorine
and
organophosphorous
pesticides.
Toxicology
(2012),
http://dx.doi.org/10.1016/j.tox.2012.09.011
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