Kumar Anoop, Sasmal D, Sharma Neelima
Department of Pharmaceutical Sciences, Birla Institute of Technology, Mesra, Ranchi, 835215, Jharkhand, India.
J Appl Toxicol. 2014 Dec;34(12):1303-10. doi: 10.1002/jat.2948. Epub 2013 Nov 12.
Deltamethrin (DLM) is a well-known pyrethroid insecticide; however, the immunotoxic effects of DLM on the mammalian system and its mechanism is still unclear. This study has been designed to first observe the binding affinity of DLM to immune cell receptors and its effects on the immune system. The docking score revealed that DLM has a strong binding affinity towards the CD4 and CD8 receptors. DLM induces apoptosis in murine thymocytes in a concentration-dependent manner. The ear\ly markers of apoptosis such as enhanced reactive oxygen species (ROS) and caspase-3 activation are evident as early as 1 h by 25 and 50 μM DLM. Glutathione (GSH) depletion has also been observed at 1 h by 50 μM DLM concentration. In cell-cycle studies using flow cytometry, the fraction of hypodiploid cells has gradually increased with all the concentrations of DLM at 18 h. The Annexin V binding assay measures the effect of DLM on apoptotic and necrotic cells. The apoptotic cells raised from 18.6% to 35.21% (10-50 μM DLM) at 18 h. N-acetyl cysteine (NAC) effectively reduced the percentage of apoptotic cells which is increased by DLM. In contrast, buthionine sulfoximine (BSO) caused an elevation in the percentage of apoptotic cells. These results demonstrate that caspase activation, ROS activation and GSH act as critical mediators in a DLM-induced apoptogenic signalling pathway in murine thymocytes. In the presence of caspase inhibitor, the percentage of apoptotic cells is partially decreased. Thus, there may be the possibility of some other caspase-independent pathways in DLM-induced apoptosis.
溴氰菊酯（DLM）是一种著名的拟除虫菊酯类杀虫剂；然而，DLM对哺乳动物系统的免疫毒性作用及其机制仍不清楚。本研究旨在首先观察DLM与免疫细胞受体的结合亲和力及其对免疫系统的影响。对接分数显示，DLM对CD4和CD8受体具有很强的结合亲和力。DLM以浓度依赖的方式诱导小鼠胸腺细胞凋亡。早在1小时，25和50μM DLM就能明显观察到凋亡的早期标志物，如活性氧（ROS）增强和半胱天冬酶-3激活。在50μM DLM浓度下，1小时也观察到谷胱甘肽（GSH）耗竭。在使用流式细胞术的细胞周期研究中，18小时时，所有浓度的DLM处理下，亚二倍体细胞分数逐渐增加。膜联蛋白V结合试验测量DLM对凋亡和坏死细胞的影响。18小时时，凋亡细胞从18.6%增加到35.21%（10 - 50μM DLM）。N - 乙酰半胱氨酸（NAC）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（BSO）导致凋亡细胞百分比升高。这些结果表明，半胱天冬酶激活、ROS激活和GSH在DLM诱导的小鼠胸腺细胞凋亡信号通路中起关键介导作用。在存在半胱天冬酶抑制剂的情况下，凋亡细胞百分比部分降低。因此，在DLM诱导的凋亡中可能存在一些其他不依赖半胱天冬酶的途径。
