van Raaij J A, Frijters C M, Kong L W, van den Berg K J, Notten W R
Institute of Public Health and Social Medicine, Erasmus University Rotterdam, The Netherlands.
Toxicology. 1994 Nov-Dec;94(1-3):197-208. doi: 10.1016/0300-483x(94)90038-8.
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.
在本研究中,研究了六氯苯(HCB)及其代谢产物五氯苯酚(PCP)对大鼠脑脊液(CSF)和脑结构摄取甲状腺素(T4)的影响。对照大鼠的脑脊液通过相对缓慢的过程摄取[125I]T4,约3小时后达到稳态。重复给予HCB和单次给予PCP均导致[125I]T4进入脑脊液、全脑组织以及特定脑结构(如枕叶皮质、丘脑和海马体)的摄取减少。尽管HCB处理导致血清中HCB和PCP水平升高,但脑中仅存在大量的HCB(血清水平的16%)。在脑脊液中,HCB和PCP的浓度均低于检测水平。然而,PCP的单独实验表明,PCP进入脑脊液的摄取呈剂量和时间依赖性。目前的结果表明,PCP和母体化合物HCB能够影响T4的脑供应。这可能对大脑的充分发育或成年人的正常脑功能产生影响。PCP和/或HCB干扰T4脑摄取的确切机制仍有待确定。