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评估静脉注射脂质乳剂对家兔氟哌啶醇诱导的神经毒性的影响及安全性。

Evaluating the effects and safety of intravenous lipid emulsion on haloperidol-induced neurotoxicity in rabbit.

作者信息

Moshiri Mohammad, Mohammadpour Amir Hooshang, Vahabzadeh Maryam, Etemad Leila, Memar Bahram, Hosseinzadeh Hossein

机构信息

Department of Pharmacodynamy and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.

Department of Pharmacodynamy and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran ; Medical Toxicology Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

Biomed Res Int. 2014;2014:949262. doi: 10.1155/2014/949262. Epub 2014 May 29.

Abstract

There are many reports on the effect of intravenous lipid emulsion (ILE) as an antidote in drugs related toxicities. We determined the effects of ILE on neurotoxicity of haloperidol (HA), a highly lipophilic antipsychotic, as a model of antipsychotics poisoning. We used six groups of five male rabbits. Two groups received distilled water intravenously followed by infusions of either 18 mL/kg of normal saline or ILE 20%, after 30 minutes. The third group received 18 mL/kg of normal saline after HA (2.6 mg/kg) administration. The three other groups received ILE 20% solution (6, 12, and 18 mL/kg) following HA injection. Catalepsy scores, temperature, pupil size, and mortality rate were measured at 0, 0.5, 1, 2, 3, 4, 8, and 24 hours after HA administration began. Blood and tissue samples were taken from all animals at 24 hours or at death time for biochemical, cell count, and pathological studies. ILE reversed cataleptic scores, miotic pupils, and hypothermia of HA intoxication much faster than normal saline (P < 0.001). Biochemical complications and mortality rate of the animals were significantly higher in the HA + 18 mL/Kg ILE group. ILE reversed sings of HA neurotoxicity; however, synergistic effect of high dose of ILE and HA increased complications and mortality.

摘要

关于静脉注射脂质乳剂(ILE)作为药物相关毒性解毒剂的作用,有许多报道。我们以抗精神病药物中毒模型,研究了ILE对高度亲脂性抗精神病药物氟哌啶醇(HA)神经毒性的影响。我们使用了六组,每组五只雄性兔子。两组静脉注射蒸馏水,30分钟后分别输注18 mL/kg生理盐水或20% ILE。第三组在给予HA(2.6 mg/kg)后输注18 mL/kg生理盐水。另外三组在注射HA后给予20% ILE溶液(6、12和18 mL/kg)。在开始给予HA后的0、0.5、1、2、3、4、8和24小时测量僵住症评分、体温、瞳孔大小和死亡率。在24小时或死亡时从所有动物采集血液和组织样本,进行生化、细胞计数和病理学研究。ILE比生理盐水更快地逆转了HA中毒的僵住症评分、瞳孔缩小和体温过低(P < 0.001)。HA + 18 mL/Kg ILE组动物的生化并发症和死亡率显著更高。ILE逆转了HA神经毒性的体征;然而,高剂量ILE与HA的协同作用增加了并发症和死亡率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d9a/4058127/2749241de411/BMRI2014-949262.001.jpg

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