Cytotoxicity analysis of alendronate on cultured endothelial cells and subcutaneous tissue. A pilot study
Cytotoxicity analysis of alendronate on cultured endothelial cells and subcutaneous tissue. A pilot study
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DOI：
10.1111/j.1600-9657.2005.00370.x
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发表时间：
2005-12-01
影响因子：
2.5
通讯作者：
Marques, MM
中科院分区：
文献类型：
--
作者：
Moreira, MS;Katayama, E;Marques, MM
阿仑膦酸盐是一种抑制骨吸收的双膦酸盐，用于防止牙齿再植后牙根吸收具有临床意义。然而，这种药物必须与根尖周围组织具有生物相容性。本研究的目的是分析阿仑膦酸钠聚乙二醇膏（2 g ml(-1)）对体外培养的内皮细胞和体内大鼠皮下组织的影响。在体外研究中，将膏体涂在浸入融合细胞培养（克隆Cips）的圆形玻璃罩上。在接触该物质0、6和12 h后，分别获得这些培养物的细胞存活率。作为对照，使用普通盖层的培养物。该分析采用台盼蓝染料排除法进行。在体内研究中，将膏体引入聚乙烯管，并将其放入大鼠皮下组织中。7、14天后处死大鼠；苏木精-伊红染色组织切片分析。与对照组相比，阿仑膦酸钠在体外培养6 h （P < 0.05）和12 h （P < 0.01）显著降低了细胞活力。在体内，组织反应旺盛，在两个实验时间相似。与导管开口端接触的大面积坏死。皮下可见微脓肿及强烈炎性浸润，并渗透肌纤维及脂肪小叶。综上所述，用聚乙二醇制备的阿仑膦酸钠膏体在体内和体外均具有较高的细胞毒性。
The use of alendronate, a bisphosphonate which is able to inhibit bone resorption, in order to prevent dental root resorption after tooth replantation would be of clinical relevance. However, this drug must be biocompatible to the periapical tissues. The aim of this study was to analyze the effect of an alendronate paste in polyethyleneglycol (2 g ml(-1)) on endothelial cells in culture (in vitro) and on rat subcutaneous tissue (in vivo). For the in vitro study the paste was applied on round glass coverslips that were immersed into confluent cell cultures (clone Cips). The cell viability percentages of these cultures were obtained 0, 6 and 12 h after contact with the substance. As control, cultures that received plain coverslips were used. This analysis was carried out in triplicate using the Trypan blue dye exclusion assay. For the in vivo study the paste was introduced into polyethylene tubes that were placed into the rat subcutaneous tissue. The rats were killed 7 and 14 days later; then, the tissue sections stained with hematoxylin-eosin were analyzed. In vitro, the alendronate caused a significant decrease in the cell viability in 6 h (P < 0.05) and 12 h (P < 0.01), when compared with the control cultures. In vivo the tissue response was exuberant and similar at the two experimental times. There was a necrosis in a comprehensive area in contact with the open end of the tube. Presence of micro-abscesses and intense inflammatory infiltrate in the hypoderm permeating the muscle fibers and fat lobules were observed. In conclusion, the alendronate paste in polyethylene glycol as used showed to be highly cytotoxic in vitro as well as in vivo.