Brain uptake of deltamethrin in rats as a function of plasma protein binding and blood-brain barrier maturation

Neurotoxicology
Manoj AmaraneniJames V Bruckner

Abstract

Pyrethroids, including permethrin and deltamethrin (DLM), are very widely used of insecticides. It was hypothesized that lower plasma binding and increased blood-brain barrier (BBB) penetration of DLM in immature rats contribute to the higher brain concentrations of DLM and more pronounced neurotoxicity reported in this age group. The left brain of anesthetized adult rats was perfused for 2min via a carotid artery with 1μM 14C-DLM in: 2-5% human serum albumin (HSA); plasma from adult and 15- and 21-d-old rats; and plasma from human donors of: birth-1 week, 1-4 weeks, 4 weeks-1 year, 1-3 years and adults. The fraction of DLM bound and brain uptake of DLM did not vary significantly with the HSA concentration nor with the age of rat or human plasma donors. One, 10 and 50μM 14C-DLM were perfused into the left-brain of anesthetized adult, 15- and 21-d-old rats. DLM deposition in the brain was linear over this range of concentrations and inversely related to age. The results of this investigation indicate that increased BBB permeability in the youngest rats enhances brain deposition of the insecticide. Plasma protein binding of DLM in immature rats and humans is not sufficiently diminished to impact its brain uptake.

Citations

Apr 27, 2017·Journal of Pharmaceutical Sciences·Manoj AmaraneniBrian S Cummings
Jul 11, 2018·Arhiv za higijenu rada i toksikologiju·Vedran Mužinić, Davor Želježić
May 19, 2018·The Journal of Physiology·Norman R SaundersMark D Habgood
Nov 23, 2017·Toxicological Sciences : an Official Journal of the Society of Toxicology·Tanzir MortuzaJames V Bruckner
Dec 7, 2019·Toxicological Sciences : an Official Journal of the Society of Toxicology·Jing PangJames V Bruckner
Dec 14, 2018·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Tanzir B MortuzaJames V Bruckner
Jun 15, 2019·Acta Neuropathologica·Jason R RichardsonAnumantha G Kanthasamy
May 10, 2020·International Journal of Environmental Research and Public Health·Jean-Noël HouchatSteeve H Thany
Apr 14, 2021·Neurotoxicology and Teratology·Emily M PitzerCharles V Vorhees

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