Rezg Raja, Mornagui Bessem, Santos Jana Sopkova-de Oliveira, Dulin Fabienne, El-Fazaa Saloua, Ben El-Haj Noomen, Bureau Ronan, Gharbi Najoua
Laboratoire de Physiologie des Agressions, Département de Biologie, Faculté des Sciences de Tunis, Université El Manar, Tunis, Tunisie.
Environ Sci Pollut Res Int. 2015 Apr;22(8):6198-207. doi: 10.1007/s11356-014-3824-5. Epub 2014 Nov 18.
Exposure to pesticides is suspected to cause human health problems. Our study aimed to evaluate preventive effects of caffeic acid (3,4-dihydroxycinnamic acid) in the hypothalamus against malathion-induced neuropeptides gene expression alterations. Malathion at 100 mg/kg was administered intragastrically to rats alone or in combination with caffeic acid at 100 mg/kg during 4 weeks. A molecular expression of hypothalamic neuropeptides and plasmatic cholinesterase activity was investigated. Furthermore, we used in silico analysis, known as computational docking, to highlight the nature of acetylcholinesterase-malathion/caffeic acid interactions. Our findings showed differences in the responses and indicate that caffeic acid reversed malathion-induced decrease in corticotropin-releasing hormone mRNA but not brain-derived neurotrophic factor which presented an increased tendency. We suggest that caffeic acid can interact with acetylcholinesterase as the primary target of organophosphorus compounds. Results predict that caffeic acid can block partly the acetylcholinesterase gorge entrance via π-π stacking interaction with Tyr 124 and Trp 286 residues of the peripheral site leading to its stricture. Under this condition, we suggested that acetylcholine trafficking toward the catalytic site is ameliorated compared to malaoxon according to their sizes.
接触农药被怀疑会引发人类健康问题。我们的研究旨在评估下丘脑内咖啡酸（3,4 - 二羟基肉桂酸）对马拉硫磷诱导的神经肽基因表达改变的预防作用。在4周内，将100毫克/千克的马拉硫磷单独或与100毫克/千克的咖啡酸联合经胃内给予大鼠。研究了下丘脑神经肽的分子表达和血浆胆碱酯酶活性。此外，我们使用了被称为计算对接的计算机模拟分析来突出乙酰胆碱酯酶 - 马拉硫磷/咖啡酸相互作用的性质。我们的研究结果显示了反应上的差异，并表明咖啡酸逆转了马拉硫磷诱导的促肾上腺皮质激素释放激素mRNA的降低，但对脑源性神经营养因子没有作用，其呈现出增加的趋势。我们认为咖啡酸可以与作为有机磷化合物主要靶点的乙酰胆碱酯酶相互作用。结果预测，咖啡酸可通过与外周位点的Tyr 124和Trp 286残基的π - π堆积相互作用部分阻断乙酰胆碱酯酶的峡谷入口，导致其狭窄。在这种情况下，我们认为与马拉氧磷相比，根据它们的大小，乙酰胆碱向催化位点的运输得到了改善。
