Enhanced renal clearance of vancomycin in rats with carcinogen-induced osteosarcoma.
Enhanced renal clearance of vancomycin in rats with carcinogen-induced osteosarcoma.
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发表时间：
2012-03
影响因子：
2
通讯作者：
Izumi Shimada;Chieko Iwata;Shino Taga;H. Teramachi;M. Nomura;K. Miyamoto;Hiroyuki Tsuciya;T. Wada;K. Kimura;R. Matsushita
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文献类型：
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作者：
Izumi Shimada;Chieko Iwata;Shino Taga;H. Teramachi;M. Nomura;K. Miyamoto;Hiroyuki Tsuciya;T. Wada;K. Kimura;R. Matsushita
最近，据报道，与无恶性肿瘤的患者相比，恶性肿瘤患者中万古霉素的总清除率（CLtot）显著更高。在本研究中，为了阐明这种恶性肿瘤增强的机制，我们采用大鼠动物模型，使用化学致癌剂诱导的骨肉瘤，选择肺转移灶（C-SLM），移植到大腿肌肉中。荷瘤大鼠对万古霉素的CLtot和肾清除率（CLr）均高于对照组。然而，肾小球滤过率无差异。荷瘤大鼠血浆IL-1 β、IL-6浓度升高。当近端肾小管上皮细胞（RPTEC）同时暴露于IL-1β、IL-6和肿瘤坏死因子（TNF）-α时，其排泄率显著增加。这些结果表明，肾小管排泄或细胞因子的重吸收可能与荷瘤大鼠中万古霉素CLtot增强的变化有关。
Recently, it has been reported that total clearance (CLtot) of vancomycin is significantly higher in patients with malignancies compared to those without malignancies. In the present study, to clarify the mechanism of this enhancement in malignancy, we adopted rat animal models, using chemical carcinogen-induced osteosarcoma, selected lung metastatic lesions (C-SLM), transplanted into thigh muscles. The CLtot and renal clearance (CLr) of vancomycin in the tumor-bearing rats were increased compared to the ones of the control rats without tumor. However, there was no difference in the glomerular filtration rate. The plasma concentrations of interleukin (IL)-1β and IL-6, were elevated in the tumor-bearing rats. When renal proximal tubular epithelial cells (RPTEC) were exposed to IL-1β, IL-6, and tumor necrosis factor (TNF)-α simultaneously, the excretory ratio increased significantly. These findings suggest that tubular excretion or re-absorption by cytokines might be associated with changes in the vancomycin CLtot enhancement in the tumor-bearing rats.