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溴氰菊酯诱导小鼠胸腺和脾脏毒性的机制及其胡椒碱和姜黄素的保护作用:体内研究

Mechanism of deltamethrin induced thymic and splenic toxicity in mice and its protection by piperine and curcumin: in vivo study.

作者信息

Kumar Anoop, Sasmal Dinakar, Sharma Neelima

机构信息

a Department of Pharmaceutical Sciences and Technology , Birla Institute of Technology, Mesra , Ranchi , India.

出版信息

Drug Chem Toxicol. 2018 Jan;41(1):33-41. doi: 10.1080/01480545.2017.1286352. Epub 2017 Feb 28.

DOI:10.1080/01480545.2017.1286352
PMID:28633599
Abstract

Deltamethrin (DLM) is a well-known pyrethroid insecticide which is widely used in the agriculture and home pest control due to restriction on the sale of organophosphate. DLM induced apoptosis is well known but its mechanism is still unclear. This study has been designed to find out its mechanism of apoptosis with the help of computational methods along with in vivo methods. The QikProp and ProTox results have shown that DLM has good oral absorption. The docking results reveal that DLM has a strong binding affinity toward the CD4, CD8, CD28 and CD45 receptors. Further, to understand the toxicity of DLM on lymphoid cells, a single dose of DLM (5 mg/kg, oral for seven days) has been administered to male Balb/c mice and cytotoxicity (MTT assay), oxidative stress indicators (glutathione, reactive oxygen species) and apoptotic markers (caspase-3 activity, DNA fragmentation) have been assessed in thymic and splenic single cell suspensions. Lowering of body weight, cellularity and loss in cell viability have been observed in DLM treated mice. The significant increase in ROS and GSH depletion in spleen and thymus, indicate the possible involvement of oxidative stress. The spleen cells appear more susceptible to the adverse effects of DLM than thymus cells. Further, for the amelioration of its effect, two structurally different bioactive herbal extracts, piperine and curcumin have been evaluated and have shown the cytoprotective effect by inhibiting the apoptogenic signaling pathways induced by DLM.

摘要

溴氰菊酯(DLM)是一种著名的拟除虫菊酯类杀虫剂,由于有机磷农药销售受限,它被广泛应用于农业和家庭害虫防治。DLM诱导细胞凋亡是已知的,但其机制仍不清楚。本研究旨在借助计算方法和体内实验方法来探究其凋亡机制。QikProp和ProTox的结果表明DLM具有良好的口服吸收性。对接结果显示DLM对CD4、CD8、CD28和CD45受体具有很强的结合亲和力。此外,为了解DLM对淋巴细胞的毒性,给雄性Balb/c小鼠单次口服DLM(5mg/kg,连续7天),并在胸腺和脾脏单细胞悬液中评估细胞毒性(MTT法)、氧化应激指标(谷胱甘肽、活性氧)和凋亡标志物(半胱天冬酶-3活性、DNA片段化)。在DLM处理的小鼠中观察到体重下降、细胞数量减少和细胞活力丧失。脾脏和胸腺中活性氧的显著增加和谷胱甘肽的消耗,表明氧化应激可能参与其中。脾脏细胞似乎比胸腺细胞更容易受到DLM的不利影响。此外,为了改善其作用效果,评估了两种结构不同的生物活性草药提取物胡椒碱和姜黄素,它们通过抑制DLM诱导的凋亡信号通路显示出细胞保护作用。

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