Szczepkowska A, Młynarczuk J, Grochowalski A, Dufourny L, Thiéry J C, Skipor J
Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Tuwima 10, 10-747 Olsztyn, Poland.
Pol J Vet Sci. 2012;15(4):621-8. doi: 10.2478/v10181-012-0098-z.
Ortho-substituted polychlorinated biphenyl (PCB) congeners, which constitute a large part of PCB residues found in the environment and in animal tissues, are known to exert potent vascular effects and can activate endothelial cells in the periphery and in the brain. The choroid plexus (CP) is responsible for cerebrospinal fluid (CSF) production and its epithelial cell layer is responsible for structure and functions of the blood-CSF barrier. The aims of this study were: 1) to investigate if environmentally relevant doses of PCB153 and similar doses of PCB104 caused changes in the expression of vascular endothelial growth factor (VEGF)--receptor system, which maintains CP function, and 2) to determine the level of both congeners in blood plasma after their oral administration. Studies of both congeners were performed on ovariectomized ewes treated per os with low doses (0.1 mg/kg, three times a week for two weeks) of PCB153 (n = 4) or PCB104 (n = 4) and vehicle (control, n = 4). The effects of PCB153 and PCB104 treatment on mRNA expression of two isoforms of VEGF (VEGF120 and VEGF164) and their receptors Flt-1 and KDR were determined using real-time PCR. Plasma concentration of PCBs was measured using high resolution chromatography/tandem mass spectrometry (HRGC/MS-MS). We observed that neither PCB153 nor PCB104 significantly altered the mRNA of the VEGF-receptor system in the CP. In PCB treated animals plasma concentration of PCB153 (1.425 +/- 0.16 ng/g of dry mass, DM) was about 150 times higher than PCB104 (0.009 +/- 0.007 ng/g DM). In control animals the PCB153 level was 0.14 +/- 0.031 ng/g DM, while the PCB104 level was below detection level. This indicates that increase in plasma PCB153 concentration to levels similar to those reported in humans and of PCB104 concentration to levels 100 times higher than those found in human plasma did not affect the VEGF-receptor system in the CP in adult ewes. The significantly lower increase of PCB104 than PCB153 concentration in blood after oral administration suggests different absorption of both congeners from the digestive tract.
邻位取代的多氯联苯（PCB）同系物在环境和动物组织中的PCB残留中占很大一部分，已知其具有强大的血管效应，可激活外周和大脑中的内皮细胞。脉络丛（CP）负责脑脊液（CSF）的产生，其上皮细胞层负责血脑屏障的结构和功能。本研究的目的是：1）研究与环境相关剂量的PCB153和类似剂量的PCB104是否会导致维持CP功能的血管内皮生长因子（VEGF）-受体系统表达发生变化；2）确定口服给药后血浆中这两种同系物的水平。对去卵巢母羊进行了这两种同系物的研究，这些母羊经口给予低剂量（0.1mg/kg，每周三次，共两周）的PCB153（n = 4）或PCB104（n = 4）以及赋形剂（对照组，n = 4）。使用实时PCR测定PCB153和PCB104处理对VEGF两种同工型（VEGF120和VEGF164）及其受体Flt-1和KDR的mRNA表达的影响。使用高分辨率色谱/串联质谱（HRGC/MS-MS）测量血浆中PCB的浓度。我们观察到，PCB153和PCB104均未显著改变CP中VEGF-受体系统的mRNA。在经PCB处理的动物中，PCB153的血浆浓度（1.425±0.16ng/g干重，DM）比PCB104（0.009±0.007ng/g DM）高约150倍。在对照动物中，PCB153水平为0.14±0.031ng/g DM，而PCB104水平低于检测限。这表明，将成年母羊血浆中PCB153浓度提高到与人类报告的水平相似，以及将PCB104浓度提高到比人类血浆中发现的水平高100倍，均未影响CP中的VEGF-受体系统。口服给药后，血液中PCB104浓度的升高明显低于PCB153，这表明两种同系物从消化道的吸收情况不同。
