Badraoui Riadh, Blouin Stéphane, Moreau Marie Françoise, Gallois Yves, Rebai Tarek, Sahnoun Zouhaier, Baslé Michel, Chappard Daniel
INSERM, U 922 - LHEA, Faculté de Médecine, 49045 Angers Cedex, France.
Chem Biol Interact. 2009 Dec 10;182(2-3):98-105. doi: 10.1016/j.cbi.2009.09.010. Epub 2009 Sep 23.
The pathophysiological changes and the oxidative-antioxidative status were evaluated in the bone microenvironment of rat inoculated with Walker 256/B mammary gland carcinoma cells, and used alpha-tocopherol acetate (ATA) as a countermeasure. Walker 256/B cells were injected into the right femora of aged male rats. Animals were randomized into three groups: 12 rats were injected with saline (control group); 14 rats were injected with Walker 256/B cells (5x10(4)) in the medullar cavity (W256 group); 14 rats were inoculated with Walker 256/B cells and treated with ATA (45mg/kg BW) (W256+ATA group). After 20 days, rats were euthanized and the femurs were radiographed. Micro architectural parameters were measured by microcomputed tomography and histology. Serum, bone and bone marrow were evaluated for oxidative damage. In parallel, cell cultures were done in the presence of ATA and ROS were measured by fluorescence; apoptotic cells were determined in parallel. W256 groups had osteolytic damages with marked resorption of cortical and trabecular bone. W256+ATA animals presented marked osteosclerotic areas associated with tumor necrosis areas inside the bone cavity. Levels of lipid peroxidation and protein oxidation were found to increase in W256 rats; a significant reduction in SOD and GSH-p activities was also observed. W256+ATA group had significantly reduced oxidative damage, but not reversed back to the control levels. The present study shows that Walker 256/B cells induce skeletal metastases associated with oxidative damage in the bone microenvironment. ATA reduced the oxidative stress damage, enhanced osteosclerosis and tumor cell apoptosis both in vitro and in vivo.
在接种Walker 256/B乳腺癌细胞的大鼠骨微环境中评估病理生理变化和氧化-抗氧化状态，并使用醋酸α-生育酚（ATA）作为对策。将Walker 256/B细胞注射到老年雄性大鼠的右股骨中。动物被随机分为三组：12只大鼠注射生理盐水（对照组）；14只大鼠在髓腔内注射Walker 256/B细胞（5×10⁴）（W256组）；14只大鼠接种Walker 256/B细胞并用ATA（45mg/kg体重）治疗（W256 + ATA组）。20天后，对大鼠实施安乐死并对股骨进行X线摄影。通过微计算机断层扫描和组织学测量微观结构参数。评估血清、骨骼和骨髓的氧化损伤。同时，在ATA存在的情况下进行细胞培养，并通过荧光测量活性氧；并行测定凋亡细胞。W256组出现溶骨性损伤，皮质骨和小梁骨明显吸收。W256 + ATA组动物在骨腔内出现与肿瘤坏死区域相关的明显骨硬化区域。发现W256大鼠的脂质过氧化和蛋白质氧化水平增加；还观察到超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-p）活性显著降低。W256 + ATA组的氧化损伤明显减轻，但未恢复到对照水平。本研究表明，Walker 256/B细胞诱导与骨微环境氧化损伤相关联的骨转移。ATA在体外和体内均降低了氧化应激损伤，增强了骨硬化和肿瘤细胞凋亡。
