Toxicokinetics and toxicodynamics of paraquat accumulation in mouse brain

Kavita Prasad, Elizabeth Tarasewicz, Jason Mathew, Pamela A.Ohman Strickland, Brian Buckley, Jason R. Richardson, Eric K. Richfield

Research output: Contribution to journalArticlepeer-review

80 Scopus citations


Paraquat (PQ) is a potential human neurotoxicant and is used in models of oxidative stress. We determined the toxicokinetics (TK) and toxicodynamics (TD) of PQ in adult mouse brain following repeated or prolonged PQ exposure. PQ accumulated in different brain regions and reached a plateau after ∼ 18 i.p. (10 mg/kg) doses and resulted in modest morbidity and mortality unpredictably associated with dose interval and number. PQ had divergent effects on horizontal locomotor behavior depending on the number of doses. PQ decreased striatal dopamine levels after the 18th to 36th i.p. dose (10 mg/kg) and reduced the striatal level of tyrosine hydroxylase. Drinking water exposure to PQ (0.03- 0.05 mg/ml) did not result in any mortality and resulted in concentration and time dependent levels in the brain. The brain half-life of PQ varied with mouse strain. PQ accumulates and may saturate a site in mouse brain resulting in complex PQ level and duration-related consequences. These findings should alter our risk assessment of this compound and demonstrate a useful, but complex dynamic model for understanding the consequences of PQ in the brain.

Original languageEnglish (US)
Pages (from-to)358-367
Number of pages10
JournalExperimental Neurology
Issue number2
StatePublished - Feb 2009

All Science Journal Classification (ASJC) codes

  • Neurology
  • Developmental Neuroscience


  • Dopamine system
  • Oxidative stress
  • Paraquat
  • Parkinson's disease
  • Toxicodynamics
  • Toxicokinetics


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