Yashwanth Bomma, Pamanji Rajesh, Rao J Venkateswara
Biology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India; Academy of Scientific and Innovative Research (AcSIR), CSIR-Indian Institute of Chemical Technology, Hyderabad, India.
Biology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India.
Aquat Toxicol. 2016 Nov;180:155-163. doi: 10.1016/j.aquatox.2016.09.018. Epub 2016 Oct 1.
This study outlines the toxic effects of Quinalphos (QP), an organophosphrous insecticide on the development of zebrafish (Danio rerio) embryos, with special emphasis on toxicomorphomics and toxicokinetics of target enzyme, AChE. A range of concentrations was used to elucidate the median lethal concentration (LC) of Quinalphos. Furthermore, embryos were exposed to two sub-lethal concentrations LC (0.66mg/L) and LC (1.12mg/L) along with a median lethal concentration (3.0mg/L) for 96h. Several morphological aberrations like lordosis, kyphosis, scoliosis, heart edema, breaks in the neuronal tube and underdeveloped facial parts were noticed, which were of concentration and time dependent. The QP has adequately hindered hatching process during the course of exposure which was upheld by the in silico docking studies with hatching enzyme, ZHE1. The length of hatchlings at 96h in LC concentration was significantly reduced to 47% compared to control. A significant pericardial effusion (5 to 16 fold) was observed in >90% of LC treated groups. Morphological changes in heart lead to the bradycardia, which ultimately leading to heart failure in some cases. The swimming behavior was significantly diminished in relation to the inhibition of AChE levels. From the in vitro kinetic studies, the kinetic constants K, V and inhibitory concentration K (4.45×10M) was determined which supported the competitive nature of QP.
本研究概述了有机磷杀虫剂喹硫磷(QP)对斑马鱼(Danio rerio)胚胎发育的毒性作用,特别强调了靶酶乙酰胆碱酯酶(AChE)的毒理形态学和毒代动力学。使用一系列浓度来阐明喹硫磷的半数致死浓度(LC)。此外,将胚胎暴露于两个亚致死浓度LC(0.66mg/L)和LC(1.12mg/L)以及一个半数致死浓度(3.0mg/L)下96小时。观察到了几种形态学异常,如脊柱前凸、脊柱后凸、脊柱侧凸、心脏水肿、神经管断裂和面部发育不全,这些异常具有浓度和时间依赖性。在暴露过程中,喹硫磷充分阻碍了孵化过程,这一点通过与孵化酶ZHE1的计算机对接研究得到了支持。与对照组相比,LC浓度下96小时的幼体长度显著缩短至47%。在>90%的LC处理组中观察到显著的心包积液(5至16倍)。心脏的形态变化导致心动过缓,在某些情况下最终导致心力衰竭。游泳行为与AChE水平的抑制相关显著降低。从体外动力学研究中,确定了动力学常数K、V和抑制浓度K(4.45×10M),这支持了喹硫磷的竞争性性质。