Kumar Anoop, Sasmal D, Bhaskar Amand, Mukhopadhyay Kunal, Thakur Aman, Sharma Neelima
Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi-835215, Jharkhand, India.
Department of Bio-Engineering, Birla Institute of Technology, Mesra, Ranchi-835215, Jharkhand, India.
Environ Toxicol. 2016 Jul;31(7):808-19. doi: 10.1002/tox.22091. Epub 2014 Dec 23.
Deltamethrin (DLM) is a well-known pyrethroid insecticide used extensively in pest control. Exposure to DLM has been demonstrated to cause apoptosis in various cells. However, the immunotoxic effects of DLM on mammalian system and its mechanism is still an open question to be explored. To explore these effects, this study has been designed to first observe the interactions of DLM to immune cell receptors and its effects on the immune system. The docking score revealed that DLM has strong binding affinity toward the CD45 and CD28 receptors. In vitro study revealed that DLM induces apoptosis in murine splenocytes in a concentration-dependent manner. The earliest markers of apoptosis such as enhanced reactive oxygen species and caspase 3 activation are evident as early as 1 h by 25 and 50 µM DLM. Western blot analysis demonstrated that p38 MAP kinase and Bax expression is increased in a concentration-dependent manner, whereas Bcl 2 expression is significantly reduced after 3 h of DLM treatment. Glutathione depletion has been also observed at 3 and 6 h by 25 and 50 µM concentration of DLM. Flow cytometry results imply that the fraction of hypodiploid cells has gradually increased with all the concentrations of DLM at 18 h. N-acetyl cysteine effectively reduces the percentage of apoptotic cells, which is increased by DLM. In contrast, buthionine sulfoxamine causes an elevation in the percentage of apoptotic cells. Phenotyping data imply the effect of DLM toxicity in murine splenocytes. In brief, the study demonstrates that DLM causes apoptosis through its interaction with CD45 and CD28 receptors, leading to oxidative stress and activation of the mitochondrial caspase-dependent pathways which ultimately affects the immune functions. This study provides mechanistic information by which DLM causes toxicity in murine splenocytes. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 808-819, 2016.
溴氰菊酯（DLM）是一种广为人知的拟除虫菊酯类杀虫剂，广泛用于害虫防治。已证明接触DLM会导致各种细胞凋亡。然而，DLM对哺乳动物系统的免疫毒性作用及其机制仍是一个有待探索的问题。为了探究这些影响，本研究旨在首先观察DLM与免疫细胞受体的相互作用及其对免疫系统的影响。对接分数显示DLM对CD45和CD28受体具有很强的结合亲和力。体外研究表明，DLM以浓度依赖的方式诱导小鼠脾细胞凋亡。早在1小时，25和50μM的DLM就能使凋亡的最早标志物如活性氧增加和半胱天冬酶3激活明显出现。蛋白质印迹分析表明，p38丝裂原活化蛋白激酶和Bax表达呈浓度依赖性增加，而在DLM处理3小时后Bcl 2表达显著降低。在3和6小时时，25和50μM浓度的DLM也观察到谷胱甘肽耗竭。流式细胞术结果表明，在18小时时，所有浓度的DLM处理下亚二倍体细胞的比例逐渐增加。N-乙酰半胱氨酸有效降低了由DLM增加的凋亡细胞百分比。相反，丁硫氨酸亚砜胺导致凋亡细胞百分比升高。表型数据暗示了DLM对小鼠脾细胞的毒性作用。简而言之，该研究表明DLM通过与CD45和CD28受体相互作用导致凋亡，从而导致氧化应激和线粒体半胱天冬酶依赖性途径的激活，最终影响免疫功能。本研究提供了DLM在小鼠脾细胞中产生毒性的机制信息。©2014威利期刊公司。《环境毒理学》31: 808 - 819，2016。
