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: 3.05). 02/2012; 33(3):575-84. DOI: 10.1016/j.neuro.2012.02.002
Source: PubMed

ABSTRACT 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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    ABSTRACT: Insulin resistance and risk of type 2 diabetes are the most important complications following exposure to organophosphorous (OPs) pesticides. Regarding the importance of liver on metabolic pathways regulation, in particular blood glucose homeostasis, we focused on liver inflammation and oxidative damages in a subchronic model of toxicity by malathion. Adult male Wistar rats of body weight 200-250g were used for the study. Malathion (200mg/kg b.w./day) was administered to rats by oral intubation for 28 days. Glycemic and insulin resistance indices, markers of liver injury, markers of inflammation and oxidative stress were assessed. Malathion-treated rats showed increased glycemia, insulinemia and glycated hemoglobin level, HOMA-IR and HOMA-β indices, plasma activities of hepatocellular enzymes, lipid peroxidation index, CD3(+)/CD4(+) and CD3(+)/CD4(+) and pro-inflammatory cytokines when decreased antioxidant status in liver was noted. Most of our study indicates that malathion promotes insulin resistance, inflammation and Hepatosteatosis in subchronic model of exposure. On the basis of biochemical and molecular findings, it is concluded that insulin resistance induced by malathion occurs through oxidative stress and related pro-inflammatory markers in a way to result in a reduced function of insulin in liver cells.
    Environmental Toxicology and Pharmacology 08/2014; 38(2):542-553. DOI:10.1016/j.etap.2014.08.007 · 1.86 Impact Factor
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    ABSTRACT: Received 26 th April 2014. Revised 26 th May 2014. On-line 7 th July 2014. Summary Organophosphorus (OP) is a large group of compounds with a wide variety of applications. The group comprises insecticides, pesticides and nematicides etc. in addition to deadly poison OP warfare chemicals like sarin and tabun. Thousands of casualties have been reported globally each year by the unintentional and intentional use of OP compounds. Uses of deadly poison OP like sarin by terrorists groups and irresponsible regimens have been documented as well. The threat always exists. The mainstream therapy includes administration of atropine, pralidoxime and bezodiazepines in addition to general supportive measures. Despite this standard therapy, the mortality rates of OP poisoning are still high. Different approaches and methodologies have been postulated and introduced as an alternative to standard therapy but none could replace the existing standard therapy. The present short review examined the possibility of usage of antihistamines as alternate to atropine. Pros and cons have been discussed. The study suggests that some of the first generation antihistamines like promethazine and diphenhydramine may be effectively used as antidote for OP poisoning depending upon the degree of poisoning. They may have several advantages like inexpensive, systematically and centrally acting anticholinergic antihistamines, readily crosses blood-brain barrier, and large quantities of the drug exist in most hospitals and pharmacies, providing a reservoir in the event of a mass casualty event. However, further clinical studies and evidences are warranted.
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    ABSTRACT: Chlorpyrifos (CPF) and profenofos (PFF) are organophosphorus (OP) insecticides that are applied seasonally in Egypt to cotton fields. Urinary trichloro-2-pyridinol (TCPy), a specific CPF metabolite, and 4-bromo-2-chlorophenol (BCP), a specific PFF metabolite, are biomarkers of exposure, while inhibition of blood butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) activities are effect biomarkers that may be associated with neurotoxicity. Urinary TCPy and BCP and blood BChE and AChE activities were measured in 37 adult Egyptian Ministry of Agriculture workers during and after 9–17 consecutive days of CPF application followed by an application of PFF (9–11 days), and a second CPF application (5 days) in 2008. During the OP applications, urinary TCPy and BCP levels were significantly higher than baseline levels, remained elevated following the application periods, and were associated with an exposure related inhibition of blood BChE and AChE. Analysis of blood AChE levels before and after the PFF application period suggests that individual workers with peak BCP levels greater than 1000 μg/g creatinine exhibited further inhibition of blood AChE with PFF application, demonstrating that PFF exposure had a negative impact on AChE activity in this highly exposed worker population. While large interindividual differences in exposure were observed throughout this longitudinal study (peak urinary BCP and peak TCPy levels for individuals ranging from 13.4 to 8052 and 16.4 to 30,107 μg/g creatinine, respectively), these urinary biomarkers were highly correlated within workers (r = 0.75, p < 0.001). This suggests that the relative exposures to CPF and PFF were highly correlated for a given worker. The variable exposures between job classification and work site suggest that job title and work location should not be used as the sole basis for categorizing OP exposures when assessing neurobehavioral and other health outcomes in Egyptian cotton field workers. Together, these findings will be important in educating the Egyptian insecticide application workers in order to encourage the development and implementation of work practices and personal protective equipment to reduce their exposure to CPF and PFF.
    International Journal of Hygiene and Environmental Health 11/2014; 218(2). DOI:10.1016/j.ijheh.2014.10.005 · 3.28 Impact Factor

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