脂肪乳剂和咖啡酸苯乙酯对急性毒死蜱中毒时神经毒性、氧化应激及乙酰胆碱酯酶活性的影响
Effects of intralipid and caffeic acid phenethyl ester on neurotoxicity, oxidative stress, and acetylcholinesterase activity in acute chlorpyriphos intoxication.
作者信息
Ozkan Umit, Osun Arif, Basarslan Kagan, Senol Serkan, Kaplan Ibrahim, Alp Harun
机构信息
Department of Neurosurgery, Medical Faculty, Dumlupinar University Kütahya, Turkey.
Department of Neurosurgery, Medical Faculty, Mustafa Kemal University Hatay, Turkey.
出版信息
Int J Clin Exp Med. 2014 Apr 15;7(4):837-46. eCollection 2014.
UNLABELLED
Chlorpyriphos is one of the most widely used organophosphate (OP) insecticide in agriculture with potential toxicity. Current post-exposure treatments consist of anti-cholinergic drugs and oxime compounds. We studied the effects of intralipid and caffeic acid phenethyl ester (CAPE) on chlorpyriphos toxicity to compose an alternative or supportive treatment for OP poisoning.
METHODS
Forty-nine rats were randomly divided into seven groups. Chlorpyriphos was administered for toxicity. Intralipid (IL) and CAPE administered immediately after chlorpyriphos. Serum acetylcholinesterase (AChE) level, total oxidant status (TOS), total antioxidant response (TAR), and histologic examination of cerebellum and brain tissue with Hematoxylin-Eosin and immunohistochemical dyes were examined.
RESULTS
Serum enzym levels showed that chlorpyriphos and CAPE inhibited AChE while IL alone had no effect, chlorpyriphos and CAPE intensifies the inhibition effect. Significant difference at AChE levels between the chlorpyriphos+IL and chlorpyriphos+CAPE verified that IL has a protective effect on AChE inhibition. TAR levels were significantly increased in all groups except chlorpyriphos group, TOS levels revealed that CAPE and IL decrease the amount of oxidative stress. Histologic examination revealed that neuronal degeneration was slightly decreased at chlorpyriphos+IL group, but CAPE had a significant effect on protection of neuronal degeneration.
CONCLUSION
The results of this study gave us three key points. 1) AChE activity is important for diagnosis of OP intoxication but it has no value for determining the neuro-degeneration. 2) CAPE inhibits AChE activity and may increase the muscarinic-nicotinic hyperactivation. Therefore it should not be used for treatment of OP intoxication. 3) IL decreases the severity of neurodegeneration and symptoms of OP intoxication and it can be used as a supportive agent.
未标记
毒死蜱是农业中使用最广泛的有机磷杀虫剂之一，具有潜在毒性。目前接触后的治疗方法包括抗胆碱能药物和肟类化合物。我们研究了脂质乳剂和咖啡酸苯乙酯（CAPE）对毒死蜱毒性的影响，以构成有机磷中毒的替代或支持性治疗方法。
方法
49只大鼠随机分为7组。给予毒死蜱以产生毒性。在给予毒死蜱后立即给予脂质乳剂（IL）和CAPE。检测血清乙酰胆碱酯酶（AChE）水平、总氧化状态（TOS）、总抗氧化反应（TAR），并用苏木精-伊红和免疫组化染料对小脑和脑组织进行组织学检查。
结果
血清酶水平显示，毒死蜱和CAPE抑制AChE，而单独使用IL则无作用，毒死蜱和CAPE增强了抑制作用。毒死蜱+IL组和毒死蜱+CAPE组之间AChE水平的显著差异证实IL对AChE抑制具有保护作用。除毒死蜱组外，所有组的TAR水平均显著升高，TOS水平显示CAPE和IL可降低氧化应激量。组织学检查显示，毒死蜱+IL组神经元变性略有减少，但CAPE对保护神经元变性有显著作用。
结论
本研究结果为我们提供了三个关键点。1） AChE活性对有机磷中毒的诊断很重要，但对确定神经变性无价值。2） CAPE抑制AChE活性，可能会增加毒蕈碱-烟碱过度激活。因此，它不应被用于治疗有机磷中毒。3） IL可降低神经变性的严重程度和有机磷中毒的症状，可作为一种支持剂使用。
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