Pyridostigmine bromide and Gulf War syndrome

Shen, Zheng-Xuan

doi:10.1016/s0306-9877(98)90081-0

Cited by 21 publications

(16 citation statements)

References 8 publications

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“…Permefhrin-induced neurotoxic changes are characterized by aggressive sparring, increased sensitivity to external stimuli and fine tremors that progresses to whole-body tremors and prostration [34,35,4]. [22] reported a decrease in grip strength and induced head and forelimb shaking.…”

Section: Discussionmentioning

confidence: 99%

“…Following treatment, the animals were maintained for 0. 5,1,2,4,8,24,48 and 72 hrs, and urine samples were collected before sacrificing to collect plasma, liver, kidney, brain and testes. The samples were analyzed for DEET and permethrin and their metabolites by HPLC.…”

Section: Discussionmentioning

confidence: 99%

“…The animals were exposed to single dose of DEET (400mg/kg, dermal in 70% ethanol) and permethrin (1.3 mg/kg, dermal in 70% ethanol), alone or in combination. Each animal was placed in metabolic cage and urine samples were collected at 2,4,8, 16,24,48, and 72 hrs after the treatment. Animals exposed to DEET alone or in combination with permethrin excreted a significantly higher levels of 8-hydroxy-2'-deoxyguanosine than controls!…”

Section: Increased Urinary Excretion Of 8-hydroxy-2'-deoxyguanosine Fmentioning

confidence: 99%

“…Exposure of rats to a single dose of DEET (400mg/kg,dermal in 70% ethanol) and permethrin (1.3 mg/kg, dermal in 70% ethanol), alone or in combination resulted in significantly higher excretion of 8-hydroxy-2'-deoxyguanosine in the animals exposed to DEET alone or in combination with permethrin than controls. 4. Studies on pharmacokinetic interactions between a single dermal dose of DEET and permethrin.…”

Section: Reportable Outcomesmentioning

confidence: 99%

“…A relatively recent study found a decrease in motor activity in male and female rats after a single dose of DEET treatment [36]. Permethrin induced behavioral changes have also been documented in animals [16].Permefhrin-induced neurotoxic changes are characterized by aggressive sparring, increased sensitivity to external stimuli and fine tremors that progresses to whole-body tremors and prostration [34,35,4]. [22] reported a decrease in grip strength and induced head and forelimb shaking.…”

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confidence: 99%

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Toxic Interactions of Prophylactic Drugs and Pesticides

Abou‐Donia¹

2003

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Approved for public release; Distribution unlimited 12b. DISTRIBUTION CODE ABSTRACT (Maximum 200 Words/The goal of the present project is to define the mechanisms of neurotoxic interactions following exposure to pyridostigmine bromide (PB, 0.13, 1.3,13 mg/gk in water, oral), DEET (4.0, 40.0, 400.0 mg/kg in ethanol, dermal), and permethrin (0.013, 0.13, 1.3 mg/kg in ethanol, dermal) in male Sprauge-Dawley rats. The results are summarized below. 1. Combined exposure to the three test compounds for 28 days, alone or with stress produced neuropathological alterations in the brain and hepatic lesions. 2. The same treatments increased the permeability of the blood brain barrier (BBB), as assessed by [ 3 H]hexamethonium iodide uptake and horseradish peroxidase (HRP) staining.3. Specific brain region exhibited decreased activity of AChE and ligand binding of m2 muscarinic acetylcholine receptors. 4. Exposure to DEET alone, or with permethrin significantly increased urinary excretion of 8-hydroxy-2'-deoxyguanosine. 5. Within 30 minutes of dermal application of 400 mg/kg DEET alone, or in combination with 1.3 mg/kg permethrin, 55% DEET and 38% permethrin was absorbed. Distribution of permethrin in tissues was slower than DEET.Combined application to both chemicals increased AUC for DEET but did not affect AUC FlasT . a of permethrin. The goal of this project is to evaluate the possible interaction between DEET, permethrin and pyridostigmine bromide (PB) and the biological and pathological consequences of such interactions. Our standing hypothesis is that combined exposure to a mixture of chemicals would have enhanced, and in some cases deterimental toxicological effects than exposure with single chemical. SUBJECT TERMS B) ApproachWe have been testing the stated hypothesis that interactions between combined chemical exposure would result in greater toxicological and pathological changes, and certain environmental modifying factors such as stress would modulate the toxic effects in combined exposure scenario. In the previous year we have carried out dose-response studies ranging from 0.1-10 x the estimated human exposure on DEET, permethrin and PB. In those studies we carried out neurobehavioral as well as neurochemical assessment following exposure to a single or multiple chemicals (See the manuscripts in Appendix). In the current studies, we have focused on the pathological consequences of sub-chronic exposure to single chemical or combined concurrent exposure. Additionally, we studied the effect of one environmental modifier, stress on the neurotoxicity associated with concurrent exposure to PB, DEET and permethrin. The pathological changes were studied by immunohistochemical evaluation of microtubule-associated protein-2 (MAP-2), glialfibrillary acidic protein (GFAP), and microglial activation by lectin binding. Furthermore, we evaluated the possible mechanism(s) of neurotoxic effects of single or combined exposure by assessing the permeability of blood-brain barrier (BBB) and evaluating 8-hydroxy-2'-deoxyguanosine by ...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Increased Urinary Excretion Of 8-hydroxy-2'-deoxyguanosine Fmentioning

confidence: 99%

Section: Reportable Outcomesmentioning

confidence: 99%

mentioning

confidence: 99%

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Toxic Interactions of Prophylactic Drugs and Pesticides

Abou‐Donia¹

2003

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Interaction of pyridostigmine and physical stress on antioxidant defense system in skeletal muscle of mice

Jagannathan

Husain

Somani

2001

J of Applied Toxicology

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Pyridostigmine bromide (PB), a reversible anticholinesterase drug, had been used against possible nerve gas exposure during the Persian Gulf War. The Gulf War veterans used PB and they were under physical stress. This study investigated the delayed and interactive effects of pyridostigmine and physical stress on the antioxidant defense system in triceps muscle of mice. Male NIH Swiss mice were divided into four groups and treated as follows: sedentary control; pyridostigmine (1.2 mg kg(-1) p.o.); exercise; and PB plus exercise. Mice were exercised for 10 weeks, but PB was administered daily during the 5th and 6th weeks. Mice were sacrificed 24 h after the last treatments and the triceps muscle was isolated and analyzed. There was a significant increase in total superoxide dismutase (CuZn-SOD + Mn-SOD) activity (141% of control) with PB plus exercise, suggesting that any influx of superoxide anions was scavenged efficiently. The Mn-SOD enzyme protein levels were reduced significantly (63% of control) by PB plus exercise. Catalase enzyme protein levels were increased significantly by exercise (132% of control) as well as by PB plus exercise (139% of control). Glutathione levels were increased significantly by exercise alone (123% of control). Pyridostigmine bromide plus exercise significantly increased the malondialdehyde concentration (124% of control) in the triceps muscle, indicating an oxidative stress response of the combination. The data indicate that a combination of PB ingestion and exercise training significantly altered the antioxidant enzyme activities, enzyme protein levels and lipid peroxidation, leading to oxidative injury. Physical stress amplified the delayed effects of PB in the skeletal muscle of mice.

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Binding of pyridostigmine bromide, N,N-diethyl- m-toluamide and permethrin, alone and in combinations, to human serum albumin

Abu-Qare

Abou‐Donia

2002

Arch Toxicol

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In this study we examined the interaction of the anti-nerve agent drug pyridostigmine bromide (PB, 3,3-dimethylaminocarbonyloxy- N-methylpyridiniyum bromide), the insect repellent DEET ( N, N-diethyl- m-toluamide), and the insecticide permethrin [3-(2,2-dichloroethyl)-2,2-dimethylcyclopropanecarboxylic acid (3-phenoxyphenyl)methyl ester] in binding to human serum albumin (HSA). Concentrations between 500 ng/ml and 10 microg/ml PB, DEET and permethrin, alone or in combination, were incubated with HSA at 37 degrees C for 60 min. Concentrations of PB, DEET and permethrin were determined using high performance liquid chromatography (HPLC). The results showed that 81.2+/-4.2%, and 84.6+/-2.5% of the initial concentration of PB was bound to HSA when incubated alone or in combination with DEET or permethrin, respectively. DEET and permethrin did not significantly interact with HSA after 1 h of incubation. Incubation of combinations of two or three compounds did not significantly alter the binding pattern of any of the compounds with HSA. These results showed that PB is highly bound to albumin protein, while the competition between PB, DEET and permethrin on binding sites of HSA as a possible site of interaction following combined administration in vivo is not likely.

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Pyridostigmine bromide and Gulf War syndrome

Cited by 21 publications

References 8 publications

Toxic Interactions of Prophylactic Drugs and Pesticides

Toxic Interactions of Prophylactic Drugs and Pesticides

Interaction of pyridostigmine and physical stress on antioxidant defense system in skeletal muscle of mice

Binding of pyridostigmine bromide, N,N-diethyl- m-toluamide and permethrin, alone and in combinations, to human serum albumin

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