Toxicology Consulting, 116 Chalk Creek Ct, Martinez, CA, USA.
Food Chem Toxicol. 2010 Jan;48(1):363-72. doi: 10.1016/j.fct.2009.10.024. Epub 2009 Oct 22.
Highly refined mineral hydrocarbons (MHCs) such as low melting point paraffin wax (LMPW) and low viscosity white oils can cause inflammatory changes in the liver and mesenteric lymph nodes (MLNs) of the Fischer-344 (F-344) rat. In contrast, only minimal MLN changes are seen in the Sprague-Dawley (S-D) rat with no changes in the liver. In this study, the response of female F-344 and S-D rats was compared after 90days dietary treatment with 0%, 0.2% or 2% LMPW. Effects in the F-344 rats were significantly greater than in the S-D rats: increased liver and splenic weights and inflammatory changes (hepatic microgranulomas) in these tissues were observed only in the F-344 rats. Microgranulomas in the MLNs were observed in both strains but the effects were substantially greater in the F-344 rats. Cellular markers of inflammation were examined in a subset of rats from each group using immunohistochemical staining. An increase in staining for CD3 (T-cells), CD8a (suppresser/cytotoxic T-cells) and CD4 (helper T-cells) correlated with an increase in lymphoid cells in the livers of treated F-344 rats. The majority of macrophages in the hepatic microgranulomas of treated F-344 rats were negative for the ED2 marker, indicating a likely origin from non-resident macrophages. Electron microscopy showed Kupffer cell hypertrophy and hyperplasia in treated F-344 rats. However, lysozyme staining (indicating activation of epithelioid macrophages) decreased with increasing granuloma size. Non-ED2 expressing cells may have been recruited but not sufficiently activated to be lysozyme positive. Inflammatory changes in the cardiac mitral valve noted in previous studies of LMPW were also seen in the F-344 rats in this study but not in the S-D rats. Chemical analysis showed that MHC accumulated in livers from treated F-344 but not S-D rats and the concentration was more than 2-fold greater in MLNs from the F-344 than from the S-D rats. The F-344 appears to be more immunologically sensitive to a number of agents than other rat strains and the results of this study suggest that this may contribute, along with pharmacokinetic differences, to the inflammatory response of F-344 rats to dietary MHCs.
高度精制的矿物烃（MHCs），如低熔点石蜡（LMPW）和低粘度白油，可引起 Fischer-344（F-344）大鼠肝脏和肠系膜淋巴结（MLNs）的炎症变化。相比之下，Sprague-Dawley（S-D）大鼠的 MLN 变化极小，肝脏无变化。在这项研究中，比较了 90 天饮食处理后雌性 F-344 和 S-D 大鼠对 0%、0.2%或 2%LMPW 的反应。F-344 大鼠的影响明显大于 S-D 大鼠：仅在 F-344 大鼠中观察到肝脏和脾脏重量增加以及这些组织中的炎症变化（肝微肉芽肿）。两种菌株的 MLN 中均观察到微肉芽肿，但 F-344 大鼠的影响要大得多。使用免疫组织化学染色检查每组大鼠的一组细胞标记物。在治疗 F-344 大鼠的肝脏中，CD3（T 细胞）、CD8a（抑制/细胞毒性 T 细胞）和 CD4（辅助 T 细胞）的染色增加与淋巴细胞的增加相关。治疗 F-344 大鼠肝内微肉芽肿中的大多数巨噬细胞对 ED2 标记物呈阴性，表明其可能来自非驻留巨噬细胞。电子显微镜显示治疗 F-344 大鼠的 Kupffer 细胞肥大和增生。然而，溶菌酶染色（表明上皮样巨噬细胞的激活）随着肉芽肿大小的增加而减少。非 ED2 表达细胞可能已被募集，但尚未充分激活而呈溶菌酶阳性。在先前 LMPW 研究中观察到的心脏二尖瓣炎症变化也在本研究中 F-344 大鼠中出现，但在 S-D 大鼠中未出现。化学分析显示，治疗 F-344 大鼠的肝脏中 MHC 积累，但 S-D 大鼠的肝脏中没有，并且 F-344 大鼠的 MLNs 中 MHC 的浓度比 S-D 大鼠的高 2 倍以上。F-344 大鼠似乎比其他大鼠品系对多种药物更具免疫敏感性，本研究结果表明，这可能与药代动力学差异一起，导致 F-344 大鼠对膳食 MHC 的炎症反应。
