Motor functions but not learning and memory are impaired upon repeated exposure to sub-lethal doses of methyl parathion

Sun, Tingting; Paul, Ian A.; Ho, Ing K.

doi:10.1007/s11373-006-9075-9

Cited by 14 publications

(9 citation statements)

References 25 publications

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“…For example, exposure to MP at 2 mg/kg/d for 10 days reduced plasma ChE activity by 30% and induced learning deficits in the MWM in rats (Castillo et al, 2002). Further examination of MP-induced learning deficits by Sun et al (2006), however, found that exposure of rats to 3 mg/kg/d MP for 21 days reduced brain region-specific ChE activity by up to 80%, yet produced no deficits in OC active avoidance conditioning. In this task, an animal is conditioned to respond to aversive stimuli, generally in the form of sound accompanied by delayed foot shock.…”

Section: Neurobehavioral Effects In Laboratory Modelsmentioning

confidence: 99%

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Neurotoxicity in Preclinical Models of Occupational Exposure to Organophosphorus Compounds

et al. 2017

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Organophosphorus (OPs) compounds are widely used as insecticides, plasticizers, and fuel additives. These compounds potently inhibit acetylcholinesterase (AChE), the enzyme that inactivates acetylcholine at neuronal synapses, and acute exposure to high OP levels can cause cholinergic crisis in humans and animals. Evidence further suggests that repeated exposure to lower OP levels insufficient to cause cholinergic crisis, frequently encountered in the occupational setting, also pose serious risks to people. For example, multiple epidemiological studies have identified associations between occupational OP exposure and neurodegenerative disease, psychiatric illness, and sensorimotor deficits. Rigorous scientific investigation of the basic science mechanisms underlying these epidemiological findings requires valid preclinical models in which tightly-regulated exposure paradigms can be correlated with neurotoxicity. Here, we review the experimental models of occupational OP exposure currently used in the field. We found that animal studies simulating occupational OP exposures do indeed show evidence of neurotoxicity, and that utilization of these models is helping illuminate the mechanisms underlying OP-induced neurological sequelae. Still, further work is necessary to evaluate exposure levels, protection methods, and treatment strategies, which taken together could serve to modify guidelines for improving workplace conditions globally.

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Section: Neurobehavioral Effects In Laboratory Modelsmentioning

confidence: 99%

“…Studies conducted by Sun et al (2006) revealed motor deficits in rat exposed to sub-lethal levels of MP, an OP known to induce neuropathies in humans. Rats administered 3 mg/kg/d MP for 21 days exhibited brain region-specific ChE activity reductions by 80% and showed decreases in basal locomotor activity.…”

Section: Neurobehavioral Effects In Laboratory Modelsmentioning

confidence: 99%

Neurotoxicity in Preclinical Models of Occupational Exposure to Organophosphorus Compounds

et al. 2017

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“…3). A number of studies have reported changes in motor activity following exposure to common OP insecticides Gordon and Mack, 2001;Sun et al, 2006). Motor activity was differentially affected in adult and aged rats following high-dose PS treatment.…”

Section: Discussionmentioning

confidence: 99%

Comparative in vivo effects of parathion on striatal acetylcholine accumulation in adult and aged rats

et al. 2007

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“…Repeated oral exposure of rabbits to methyl parathion (1.78 mg/kg/day for 28 days) was associated only with decreased body weight gain and slightly decreased plasma acetylcholinesterase activity by day 21 (456). When rats were given subcutaneous injections of 3 mg/kg/day for 21 days, they showed cholinergic signs (tremors, purposeless chewing, and irritability), decreased body weight gain, and decreased motor activity, but no effect on active-avoidance learning (465).…”

Section: Chronic and Subchronicmentioning

confidence: 99%

Organophosphorus Pesticides

Storm¹

2012

Patty's Toxicology

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Most organophosphorus compounds today fall into two general groups: the so‐called nerve agents, that are very acutely toxic and organophosphorus pesticides that are less toxic. Nerve agents were generally the first toxic organophosphorus developed, and were the original basis for organophosphorus pesticides. Interest about nerve agents has increased lately given concerns about their potential use in terrorist acts. Organophosphate nerve agents and pesticides are a highly diverse group of chemicals. They are all characterized by their ability to inhibit the enzyme acetylcholinesterase (AChE) that deactivates the neurotransmitter acetylcholine (ACh). At present, the widest use of organophosphorus compounds is as pesticides, although they have also been used as therapeutic agents, gasoline additives, hydraulic fluids, cotton defoliants, fire retardants, plastic components, growth regulators, and industrial intermediates to a much smaller extent. Compounds in this class are numerous and have been categorized in many ways according to the nature of the substituents. Gallo and Lawryk (1991) [2], for example, categorized them into four main groups I–IV based on the characteristics of the leaving group (X). Group I compounds, phosphorylcholines, have a leaving group that contains a quaternary nitrogen and are among the most potent organophosphates (e.g., Shradan). Group II compounds, fluorophosphates, have a fluoride leaving group and are also generally highly toxic (e.g., diisopropyl fluorophosphate). Group III compounds have leaving groups that contain cyanide or a halogen other than fluoride and are generally less potent than group I or II (e.g., Parathion). Group IV contains most of the organophosphates used as insecticides today. These compounds have alkoxy, alkylthio, aryloxy, arylthio, or heterocyclic leaving groups and a wide variety of other substituents. Another classification scheme is based on the nature of the atoms that immediately surround the central phosphorus atom and results in 14 different categories. According to this scheme, phosphates are the prototype for the entire class and are those compounds where all four atoms that surround the phosphorus atom are oxygen (e.g., dichlorvos, mevinphos). Sulfur‐containing organophosphate compounds (phosphorothioates, phosphorothiolates, phosphorodithioates, and phosphorodithiolates) are far more numerous than phosphates and include well‐recognized organophosphate insecticides such as parathion, diazinon, chlorpyrifos, etc. Other groups contain nitrogen (phosphoramides and phosphorodiamides), nitrogen and sulfur (phosphoramidothionates and phosphoramidothiolates), carbon (phosphonates and phosphinates), or carbon and sulfur (phosphonothionates, phosphonothionothiolates, and phosphinothionates). All aspects of organophosphate chemistry, toxicity, analysis, and exposure potential have been previously and comprehensively reviewed. In addition, information regarding the toxicity of organophosphorus pesticides in particular has expanded greatly in recent years as a result of toxicity data supplied by registrants to the U.S. EPA's Office of Pesticides to support reregistration. These data have been made publicly available by the U.S. EPA on its Internet Web site ( www.epa.gov/pesticides ). The following discussion draws heavily from recent reviews and also includes summaries of relevant toxicity data submitted to, and made available by, the U.S. EPA.

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Motor functions but not learning and memory are impaired upon repeated exposure to sub-lethal doses of methyl parathion

Cited by 14 publications

References 25 publications

Neurotoxicity in Preclinical Models of Occupational Exposure to Organophosphorus Compounds

Neurotoxicity in Preclinical Models of Occupational Exposure to Organophosphorus Compounds

Comparative in vivo effects of parathion on striatal acetylcholine accumulation in adult and aged rats

Organophosphorus Pesticides

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