Age Dependency of Blood-Brain Barrier Penetration by cis- and trans-Permethrin in the Rat
| Autor: | James V. Bruckner, Gaylen L. Edwards, Tanzir Mortuza, Catherine A. White, Vandan Patel, Brian S. Cummings |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Pharmacology Pyrethroid Albumin Pharmaceutical Science 03 medical and health sciences chemistry.chemical_compound Dose–response relationship 030104 developmental biology 0302 clinical medicine chemistry Permeability (electromagnetism) medicine Potency 030217 neurology & neurosurgery Cis–trans isomerism Barrier function Permethrin medicine.drug |
| Zdroj: | Drug Metabolism and Disposition. 47:234-237 |
| ISSN: | 1521-009X 0090-9556 |
| DOI: | 10.1124/dmd.118.084822 |
| Popis: | Permethrin (PER), a type I pyrethroid, is the most widely used insecticide in domestic settings in the United States. The overall objective of this study was to assess the efficiency of the blood-brain barrier (BBB) as an obstacle to the 14C-cis-permethrin (CIS) and 14C-trans-permethrin (TRANS) isomers of PER, and to determine whether its barrier function changes during maturation of the rat. Experiments were conducted to quantify brain uptake of CIS and TRANS in postnatal day 145, 21, and 90 Sprague-Dawley rats. The common carotid artery of anesthetized rats was perfused for 2 or 4 minutes with 1, 10, or 50 µM 14C-CIS or 14C-TRANS in 4% albumin. Brain deposition of each isomer was inversely related to age, with levels in the youngest animals >5 times those in adults. Brain uptake was linear over the 50-fold range of pyrethroid concentrations, indicative of passive, nonsaturable BBB permeation. The extent of uptake of toxicologically relevant concentrations of CIS and TRANS was quite similar. Thus, dissimilar BBB permeation does not contribute to the greater acute neurotoxic potency of CIS, but greater permeability of the immature BBB to CIS and TRANS may contribute to the increased susceptibility of preweanling rodents to the insecticides. |
| Databáze: | OpenAIRE |
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