Banks CN, Lein PJ. A review of experimental evidence linking neurotoxic organophosphorus compounds and inflammation

Department of Molecular Biosciences, UC Davis School of Veterinary Medicine, One Shields Ave., Davis, CA 95616, USA.
NeuroToxicology (Impact Factor: 3.38). 02/2012; 33(3):575-84. DOI: 10.1016/j.neuro.2012.02.002
Source: PubMed


Organophosphorus (OP) nerve agents and pesticides inhibit acetylcholinesterase (AChE), and this is thought to be a primary mechanism mediating the neurotoxicity of these compounds. However, a number of observations suggest that mechanisms other than or in addition to AChE inhibition contribute to OP neurotoxicity. There is significant experimental evidence that acute OP intoxication elicits a robust inflammatory response, and emerging evidence suggests that chronic repeated low-level OP exposure also upregulates inflammatory mediators. A critical question that is just beginning to be addressed experimentally is the pathophysiologic relevance of inflammation in either acute or chronic OP intoxication. The goal of this article is to provide a brief review of the current status of our knowledge linking inflammation to OP intoxication, and to discuss the implications of these findings in the context of therapeutic and diagnostic approaches to OP neurotoxicity.

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    • "(A) Oxidative stress and related mechanisms and (B) inhibition of esterases. ", increase; Th2, T helper 2. cancer and certain infections would be functional consequences of chronic OP poisoning (Banks & Lein, 2012; Tarkowski et al., 2004) (Figure 1B). "
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    ABSTRACT: Nowadays, in many communities, there is a growing concern about possible adverse effects of pesticides on human health. Reports indicate that during environmental or occupational exposure, pesticides can exert some intense adverse effects on human health through transient or permanent alteration of the immune system. There is evidence on the relation between pesticide-induced immune alteration and prevalence of diseases associated with alterations of the immune response. In the present study, direct immunotoxicity, endocrine disruption and antigenicity have been introduced as the main mechanisms working with pesticides-induced immune dysregulation. Moreover, the evidence on the relationship between pesticide exposure, dysregulation of the immune system and predisposition to different types of psychiatric disorders, cancers, allergies, autoimmune and infectious diseases are criticized.
    Toxicology Mechanisms and Methods 03/2015; 11(4). DOI:10.3109/15376516.2015.1020182 · 0.75 Impact Factor
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    • "Occupational exposure to OPs has been shown to adversely affect neurobehavioral performance in multiple studies (Rohlman et al., 2011) though biological marker measures are rarely correlated with neurobehavioral performance. Biological markers including BuChE may not be sensitive enough for measuring repeated low levels of exposure, or OP/CBs may be targeting proteins other than ChEs resulting in inflammation and subsequent neurological effects (Banks and Lein, 2012). In addition, other factors, such as gender, age, physical activity, or weight, may impact BuChE levels (Lepage et al., 1985; Zimmer et al., 2012). "
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    ABSTRACT: Objectives: Organophosphate (OP) and N-methyl-carbamate (CB) insecticides are used widely in agriculture to manage insect pests of economic importance. Agricultural workers are more likely to suffer exposure because of the widespread use of OP/CBs in agriculture, and pesticide-related illnesses among handlers may be more severe when compared to other farm workers. The goal of this study was to identify occupational and personal characteristics associated with butyrylcholinesterase (BuChE) inhibition in participants recruited from the Washington State Cholinesterase Monitoring Program from 2006 to 2011.
    Annals of Occupational Hygiene 09/2014; 59(1). DOI:10.1093/annhyg/meu072 · 2.10 Impact Factor
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    • "These considerations suggest the presence of a different pathway in the neurotoxicity of these compounds . Indeed, in literature PCB neurotoxicity has been related to many different mechanisms: it has been proposed their ability to alter patterns of ryanodine receptors (RyRs) expression in brain, altering calcium flux in excitable cells (Pessah et al., 2010; Kim et al., 2011); it has been suggested pollutants ability to induce an inflammatory phenomena in neurons, altering their function and inducing neurotoxicity (Banks and Lein, 2012); lastly, PCB are able to disrupt some epigenetic markers related to chromatin remodeling favoring or silencing the translation of genes important for neuronal development and function (Casati et al., 2012). "
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    ABSTRACT: Perinatal polychlorinated biphenyl (PCB) exposures still remain a serious health concern because offspring receive PCB burden from mother during vulnerable processes of development. Since cytochrome P450 (CYP) represents a toxicological endpoint, in the present study, representing an extended investigation of a previous multitasked one, we explored the long-term responsiveness of CYP1A and CYP2B isoforms by Western blot analysis in liver and whole brain of lactating (PN12), weaning (PN21), and adult offspring (PN60) rats prenatally and lactationally exposed to a reconstituted PCB mixture (RM) of noncoplanar PCB138, 153, 180, and coplanar PCB126 congeners. We chose highly chlorinated PCBs instead of lower chlorinated one, because their recalcitrance to biotransformation makes easy their accumulation/persistence in tissues and breast milk. Dioxin-like congener PCB126 binding aryl hydrocarbon receptor (AHR) is responsible of many toxic effects. Pregnant Sprague-Dawley dams with high affinity AHR received subcutaneous injection of RM (10 mg/kg body weight) daily during gestation (days 15-19) and twice a week during breast-feeding. The results evidenced a transfer of PCBs to neonates through milk and a significant responsiveness of hepatic CYP in both mothers and offspring. In liver of exposed progeny, CYP isoforms exhibited a significant increment at PN12 (70% over control) and at PN21 (270% over control). Contrary to dams, in adult PCB offspring CYP levels showed a decline up to values similar to those of control. This transient developmental responsiveness of CYP isoforms in offspring liver reflects roughly the time course of hepatic PCB levels previously reported. Even if congeners were detected in brain, we failed in evidencing a responsiveness of CYP isoforms probably because of region-specific CYP expression in this organ. In conclusion, induction of offspring hepatic CYP is index of liver PCB burden, and despite the insensitivity of whole brain CYP we cannot exclude brain vulnerability toward PCB. © 2012 Wiley Periodicals, Inc. Environ Toxicol, 2012.
    Environmental Toxicology 08/2014; 29(8). DOI:10.1002/tox.21812 · 3.20 Impact Factor
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