Darnerud Per Ola, Wong Jennie, Bergman Ake, Ilbäck Nils-Gunnar
Toxicology Division, National Food Administration, SE-751 26 Uppsala, Sweden.
Toxicology. 2005 Jun 1;210(2-3):159-67. doi: 10.1016/j.tox.2005.01.015.
A murine model infection with the human coxsackievirus B3 (CB3) has been shown to change uptake and tissue distribution of several environmental pollutants, in some cases followed by an aggravated disease. In this study, the model was tested for polybrominated diphenyl ethers (PBDEs), which we know are absorbed from the gastro-intestinal tract and further distributed throughout the body. On day 0, female Balb/c mice were infected with CB3; on day 1 of the infection, they were dosed orally with approximately 200 microg/kgbody weight (bw) (ca. 0.52 microCi) of 14C-labelled 2,2',4,4',5-pentabromodiphenyl ether (14C-BDE-99); and on day 3 of the infection, they were sacrificed for studies of 14C-BDE-99 distribution. In comparison with control values, 14C-BDE-99 concentrations were altered in the liver (186%, p < 0.05), lungs (47%, p < 0.05) and pancreas (51%, p < 0.05), but no change was seen in the blood, brain, heart, spleen, thymus or kidneys. Moreover, on day 3, plasma thyroxine (T4) levels (33%, p < 0.001), as well as ethoxyresorufin-O-dealkylase (EROD) (17%, p < 0.001) and pentoxyresorufin O-dealkylase (PROD) (31%, p < 0.001) activities were much lower in infected compared to non-infected control mice. It is suggested that the change in tissue distribution of 14C-BDE-99 as a result of the infection may be caused by an infection-induced specific change in the hepatic enzyme activities affecting this PBDE congener. The mechanism for virally induced T4 changes remains, however, unclear. The presented infection-induced alteration in distribution, which is different from other environmental pollutants (e.g., dioxin, acrylamide and cadmium), may have consequences for PBDEs toxicity, especially in relation to microsomal enzyme and thyroid hormone activities.
已证明，用人柯萨奇病毒B3（CB3）感染小鼠的模型会改变几种环境污染物的摄取和组织分布，在某些情况下还会导致病情加重。在本研究中，对该模型进行了多溴二苯醚（PBDEs）测试，我们知道PBDEs可从胃肠道吸收并进一步分布于全身。在第0天，雌性Balb/c小鼠感染CB3；在感染的第1天，给它们口服约200微克/千克体重（bw）（约0.52微居里）的14C标记的2,2',4,4',5-五溴二苯醚（14C-BDE-99）；在感染的第3天，将它们处死以研究14C-BDE-99的分布。与对照值相比，肝脏（186%，p<0.05）、肺（47%，p<0.05）和胰腺（51%，p<0.05）中的14C-BDE-99浓度发生了变化，但血液、脑、心脏、脾脏、胸腺或肾脏中未观察到变化。此外，在第3天，与未感染的对照小鼠相比，感染小鼠的血浆甲状腺素（T4）水平（33%，p<0.001）以及乙氧基异吩恶唑酮-O-脱烷基酶（EROD）（17%，p<0.001）和戊氧基异吩恶唑酮O-脱烷基酶（PROD）（31%，p<0.001）活性要低得多。据推测，感染导致的14C-BDE-99组织分布变化可能是由感染诱导的肝脏酶活性特定变化引起的，这种变化影响了这种多溴二苯醚同系物。然而，病毒诱导T4变化的机制仍不清楚。所呈现的感染诱导的分布变化与其他环境污染物（如二恶英、丙烯酰胺和镉）不同，可能会对多溴二苯醚的毒性产生影响，尤其是与微粒体酶和甲状腺激素活性有关。
