Department of Pharmaceutical Science and Technology, Birla Institute of Technology, Mesra, Ranchi, 835215, Jharkhand, India.
Department of Pharmaceutical Science and Technology, Birla Institute of Technology, Mesra, Ranchi, 835215, Jharkhand, India.
Environ Toxicol Pharmacol. 2015 Mar;39(2):504-14. doi: 10.1016/j.etap.2014.12.021. Epub 2015 Jan 8.
Deltamethrin (DLM), a well-known pyrethroid insecticide, is a potent immunotoxicant. In rodents, it is primarily characterized by marked thymic apoptosis. Mechanism of DLM induced thymic apoptosis in primary murine thymocytes has been recently explored. Oxidative stress and activation of caspase dependent pathways appear to be involved in the DLM induced thymic injury. Thus, for the amelioration of its effect, this study has been designed to first observe the binding affinity of piperine to immune cell receptors and its protective effects on the DLM induced immunotoxicity under in vitro condition. The docking results demonstrated that piperine has good binding affinity towards CD4 and CD8 receptors. In vitro study results have shown that piperine (1, 10 and 50 μg/ml) increased cell viability in a concentration dependent manner. The early activated markers of apoptosis such as enhanced reactive oxygen species (ROS) and caspase-3 activation by DLM was significantly reduced by piperine treatment. GSH depletion induced by DLM has been also restored by piperine treatment. At 18 h, all concentration of piperine (1, 10 and 50 μg/ml) significantly ameliorated the DLM induced apoptosis. Further, DLM induced phenotypic changes were mitigated by the piperine. In addition, piperine also restored the cytokine levels, which were suppressed by DLM treatment. These findings strongly indicate the anti-oxidative, anti-apoptotic and chemo-protective ability of piperine in the DLM induced thymic apoptosis.
溴氰菊酯（DLM）是一种著名的拟除虫菊酯类杀虫剂，是一种有效的免疫毒性物质。在啮齿动物中，它主要表现为明显的胸腺细胞凋亡。最近已经探索了 DLM 诱导原代小鼠胸腺细胞凋亡的机制。氧化应激和半胱天冬酶依赖性途径的激活似乎参与了 DLM 诱导的胸腺损伤。因此，为了减轻其影响，本研究首先观察了胡椒碱与免疫细胞受体的结合亲和力及其在体外条件下对 DLM 诱导的免疫毒性的保护作用。对接结果表明，胡椒碱对 CD4 和 CD8 受体具有良好的结合亲和力。体外研究结果表明，胡椒碱（1、10 和 50μg/ml）以浓度依赖的方式增加细胞活力。DLM 诱导的早期凋亡标志物如增强的活性氧（ROS）和半胱天冬酶-3 激活明显被胡椒碱处理所降低。由 DLM 诱导的 GSH 耗竭也被胡椒碱处理所恢复。在 18 小时时，胡椒碱的所有浓度（1、10 和 50μg/ml）均显著改善了 DLM 诱导的凋亡。此外，胡椒碱还减轻了 DLM 诱导的表型变化。此外，胡椒碱还恢复了被 DLM 处理抑制的细胞因子水平。这些发现强烈表明胡椒碱在 DLM 诱导的胸腺细胞凋亡中具有抗氧化、抗凋亡和化学保护作用。
