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首页> 外文期刊>Journal of applied toxicology >Protective effect of metoclopramide against organophosphate-induced apoptosis in the murine skin fibroblast 1929
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Protective effect of metoclopramide against organophosphate-induced apoptosis in the murine skin fibroblast 1929

机译：甲氧氯普胺对鼠皮肤成纤维细胞有机磷酸酶诱导细胞凋亡的保护作用1929

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Abstract This study was performed to evaluate the protective efficacy of metoclopramide (MCP) against the organophosphates paraoxon (POX)- and malathion (MLT)-induced apoptosis in the murine L929 skin fibroblasts. L929 cells were exposed to either POX (10 nM) or 1.0 mu.M MLT in the absence and presence of increased concentrations of MCP. The protective effect of MCP on these organophosphate-stimulated apoptotic events was evaluated by flow cytometry analysis after staining with annexin-V/propidium iodide, processing and activation of the executioner caspase-3, cleavage of the poly-ADP ribose polymerase, fragmentation of the nucleosomal DNA and disruption of the mitochondrial membrane potential (DELTAPSI). Our results showed that increased doses of MCP alone (>10 mu.M) did not induce apoptosis or activation of caspase-3. Pretreatment of the cells with MCP attenuated all the apoptotic events triggered by the organophosphate compounds in a dose-dependent manner reaching -70-80% protection when they were preincubated at 1 and 5 mu.M of the drug before the addition of POX and MLT, respectively. Interestingly, MCP did not offer a significant protective effect against the cytotoxicity of tumor necrosis factor-alpha, cisplatinum, etoposide or paclitaxel, which stimulate apoptosis by various mechanisms, suggesting that the anti-apoptotic effect of the drug is specific to organophosphates. The strong and specific anti-apoptotic activity of subclinical doses of MCP against the cytotoxicity of organophosphate compounds suggests its potential clinical application in treating their poisoning.
机译：摘要进行该研究以评价甲氧丙烷烃（MCP）对鼠L929皮肤成纤维细胞中的细胞磷酸亚毒素（POX）和马他磷酸酯（MLT）的保护效果。在不存在和存在的情况下，将L929细胞暴露于POx（10nm）或1.0mOmmLT。通过用膜蛋白-V /碘化丙酸碘化物，加工和活化染色后，通过流式细胞术分析评估MCP对这些有机磷酸刺激的凋亡事件的保护作用，对脱胆汁胱天冬酶-3的加工和激活，裂解聚-ADP核糖聚合酶，碎裂核体DNA和线粒体膜电位的破坏（deltapsi）。我们的研究结果表明，单独的MCP（> 10慕=）没有诱导Caspase-3的凋亡或活化。用MCP预处理细胞以剂量依赖性方式衰减由有机磷酸酯化合物触发的所有凋亡事件，当在添加POX和MLT之前在药物1和5mom.mmm中预先孵育时达到-70-80％的保护， 分别。有趣的是，MCP对肿瘤坏死因子-α的细胞毒性没有提供显着的保护作用，即通过各种机制刺激细胞凋亡的细胞毒性，这表明药物的抗凋亡作用是有机磷的特异性。亚临床剂量MCP对有机磷酸盐化合物细胞毒性的强大和特异性抗凋亡活性表明其潜在的临床应用治疗它们的中毒。

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