Paraquat pharmacokinetics using a subcutaneous toxic low dose in the rat

Dey, Michael; Breeze, R. G.; Hayton, William L.; Karara, Adel H.; Krieger, Robert I.

doi:10.1016/0272-0590(90)90246-g

Cited by 29 publications

(9 citation statements)

References 17 publications

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“…Other studies using radiolabeled PQ found that it was absorbed by all exposure routes tested, including intravenous, intragastric, dermal, and pulmonary (Chui et al 1988; Dey et al 1990). PQ in brain after oral dosing was previously demonstrated in rat and the concentration was higher after 10 doses compared with 1, supporting its accumulation (Widdowson et al 1996).…”

Section: Discussionmentioning

confidence: 95%

“…The reason for this persistence in brain in contrast to that in other organs is not known, but this persistence may contribute to its prolonged adverse effects. PQ elimination in laboratory animals and humans from blood and organs other than the brain has always been reported in hours and days (Dey et al 1990; Houze et al 1990). It is unclear if the slow loss of PQ from the VM was due to metabolism, export, or both.…”

Section: Discussionmentioning

confidence: 99%

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Prolonged Toxicokinetics and Toxicodynamics of Paraquat in Mouse Brain

Prasad

Winnik

Thiruchelvam

et al. 2007

Environ Health Perspect

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BackgroundParaquat (PQ) has been implicated as a risk factor for the Parkinson disease phenotype (PDP) in humans and mice using epidemiologic or experimental approaches. The toxicokinetics (TK) and toxicodynamics (TD) of PQ in the brain are not well understood.ObjectivesThe TK and TD of PQ in brain were measured after single or repeated doses.MethodsBrain regions were analyzed for PQ levels, amount of lipid peroxidation, and functional activity of the 20S proteasome.ResultsParaquat (10 mg/kg, ip) was found to be persistent in mouse ventral midbrain (VM) with an apparent half-life of approximately 28 days and was cumulative with a linear pattern between one and five doses. PQ was also absorbed orally with a concentration in brain rising linearly after single doses between 10 and 50 mg/kg. The level of tissue lipid peroxides (LPO) was differentially elevated in three regions, being highest in VM, lower in striatum (STR), and least in frontal cortex (FCtx), with the earliest significant elevation detected at 1 day. An elevated level of LPO was still present in VM after 28 days. Despite the cumulative tissue levels of PQ after one, three, and five doses, the level of LPO was not further increased. The activity of the 20S proteasome in the striatum was altered after a single dose and reduced after five doses.ConclusionsThese data have implications for PQ as a risk factor in humans and in rodent models of the PDP.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Prolonged Toxicokinetics and Toxicodynamics of Paraquat in Mouse Brain

Prasad

Winnik

Thiruchelvam

et al. 2007

Environ Health Perspect

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“…In such situations lungs are usually the most affected organ since they actively accumulate this substance through the polyamine transporter [46]. After peripheral administration of PQ, the most of the dose is taken up by the peripheral organs and remains in the blood, only a small proportion reaches the brain [47]. So, it would be expected that if oxidative stress is generated it would be of greater intensity in the periphery than in the brain.…”

Section: Ros In the Peripheral Tissuesmentioning

confidence: 98%

Increased Reactive Oxygen Species Production in the Brain After Repeated Low-Dose Pesticide Paraquat Exposure in Rats. A Comparison with Peripheral Tissues

et al. 2010

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The pesticide paraquat (PQ) was found to be a suitable xenobiotic to model Parkinson's disease. The reactive oxygen species (ROS) production was suggested to be the main cause of PQ toxicity but very few evidences were found for its generation in the brain in vivo after ip administration. We compared the effects of PQ-induced ROS generation between the brain structures and the peripheral tissues using two different hydroxyl radical generation markers. Repeated but not single ip PQ administration increased the levels of ROS in the striatal homogenates but, when measured in the extracellular microdialysis filtrate, no change was observed. The increased dopamine release was detected in the striatum after the fourth PQ administration and its basal levels were decreased. A single treatment with the pesticide did not influence ROS production in the lungs or kidneys but repeated intoxication decreased its levels. These results suggest that repeated, systemic administration of a low dose of PQ triggers intracellular ROS formation in the brain and can cause slowly progressing degenerative processes, without the toxic effects in the peripheral tissues.

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“…Also, a mean biological half-life of paraquat with subcutaneous injection was 40.9 h in an animal study (8). However, the excretion of paraquat through the kidney can damage the proximal renal epithelial cells resulting in acute renal failure due to the nephrotoxicity of paraquat.…”

Section: Discussionmentioning

confidence: 98%

Comparison of a Pulsatile Blood Pump and a Peristaltic Roller Pump During Hemoperfusion Treatment in a Canine Model of Paraquat Poisoning

et al. 2008

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This study examined the treatment efficacy and the damage to the blood during hemoperfusion for treating paraquat poisoning using two blood pump mechanisms. Paraquat-poisoned animal models were prepared. A conventional hemodialysis machine, AK90, with a peristaltic roller pump and a cardiopulmonary support system, T-PLS, with a pulsatile blood pump were used during the animal experiments. A total of 12 dogs were treated with hemoperfusion using a charcoal column. Six dogs were treated with hemoperfusion and T-PLS, and the other six were treated with AK90. A paraquat dose of 30 mg/kg was administrated by an intravenous injection. Both pumps maintained blood flow rates of 125 mL/min measured by an ultrasonic flowmeter. For anticoagulation, heparin was administrated by an initial bolus (250 IU/kg) and a continuous injection (100 IU/kg/h). During the experiments, T-PLS and AK90 showed a similar toxin removal efficacy. Both devices decreased the plasma paraquat concentration to 10% of the initial dose within 4-h hemoperfusion. The two pumps showed similar hemolysis properties with acceptable levels. Although T-PLS was developed as a cardiopulmonary bypass system, it can also be used as a hemoperfusion treatment device.

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Paraquat pharmacokinetics using a subcutaneous toxic low dose in the rat

Cited by 29 publications

References 17 publications

Prolonged Toxicokinetics and Toxicodynamics of Paraquat in Mouse Brain

Prolonged Toxicokinetics and Toxicodynamics of Paraquat in Mouse Brain

Increased Reactive Oxygen Species Production in the Brain After Repeated Low-Dose Pesticide Paraquat Exposure in Rats. A Comparison with Peripheral Tissues

Comparison of a Pulsatile Blood Pump and a Peristaltic Roller Pump During Hemoperfusion Treatment in a Canine Model of Paraquat Poisoning

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