Reduction of thyroxine uptake into cerebrospinal fluid and rat brain by hexachlorobenzene and pentachlorophenol.
In the present study the effects of hexachlorobenzene (HCB) and the metabolite pentachlorophenol (PCP) were investigated with respect to uptake of thyroxine (T4) into cerebrospinal fluid (CSF) and brain structures of rats. [125I]T4 was taken up into CSF of control rats by a relatively slow process, reaching a steady state after about 3 h. Both repeated dosing of HCB and single doses of PCP caused decreased uptake of [125I]T4 into CSF, total brain tissue as well as specific brain structures, such as occipital cortex, thalamus, and hippocampus. Although HCB-treatment caused a build-up of HCB and PCP levels in serum in brain only HCB was present in significant amounts (16% of the serum level). In CSF, both HCB and PCP concentrations were below detection levels. Separate experiments with PCP showed, however, a dose- and time-dependent uptake of PCP into CSF. The present results indicate that PCP and the parent compound HCB are able to affect brain supply of T4. This may have consequences for an adequate development of the brain or proper brain function in adults. The exact mechanisms of interference of PCP and/or HCB in brain uptake of T4 remain to be established.
van Raaij
J A
JA
Institute of Public Health and Social Medicine, Erasmus University Rotterdam, The Netherlands.
Frijters
C M
CM
Kong
L W
LW
van den Berg
K J
KJ
Notten
W R
WR
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D006581:Hexachlorobenzene / Q000494:pharmacology*; D008297:Male; D010416:Pentachlorophenol / Q000494:pharmacology*; D011228:Prealbumin / Q000378:metabolism; D051381:Rats; D013974:Thyroxine / Q000134:cerebrospinal fluid / Q000378:metabolism*
D011228:Prealbumin; D006581:Hexachlorobenzene; D010416:Pentachlorophenol; D013974:Thyroxine