Ghadiri Ameneh, Etemad Leila, Moshiri Mohammad, Moallem Seyed Adel, Jafarian Amir Hossein, Hadizadeh Farzin, Seifi Mahmoud
Department of Toxicology, Faculty of Pharmacy, Islamic Azad University, Shahreza Branch, Shahreza, Iran.
Pharmaceutical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
Iran J Basic Med Sci. 2017 Feb;20(2):138-144. doi: 10.22038/ijbms.2017.8236.
The increasing use of methamphetamine (METH) in the last decades has made it the second most abused drug. Advancs in the area of intravenous lipid emulsion (ILE) have led to its potential application in the treatment of poisoning. The present study aims to investigate the potential role of ILE as an antidote for acute METH poisoning.
Two groups of six male rats were treated by METH (45 mg/kg), intraperitoneally. Five to seven min later, they received an infusion of 18.6 ml/kg ILE 20% through the tail vein or normal saline (NS). Locomotor and behavioral activity was assessed at different time after METH administration. Body temperature and survival rates were also evaluated. Brain and internal organs were then removed for histological examination and TUNEL assay.
ILE therapy for METH poisoning in rats could prevent rats mortalities and returned the METH-induced hyperthermia to normal rates (<0.05). ILE reduced freezing and stereotyped behaviors and increased rearing responses (<0.05). Locomotor activity also returned to control levels especially during the last hours of the experiment. ILE administration decreased the prevalence of pulmonary emphysema in the lungs (<0.05 and P<0.01) and percentages of TUNEL positive cells in the brain (<0.05), in comparison with the control group.
ILE could reduce the severity of METH- induced toxicity as well as mortality rate in the animals. Intravenous infusion of lipid emulsion may save the life of patients with acute METH intoxication who do not respond to standard initial therapy.
在过去几十年中,甲基苯丙胺(METH)的使用日益增加,使其成为第二大滥用药物。静脉注射脂质乳剂(ILE)领域的进展已使其在中毒治疗中具有潜在应用价值。本研究旨在探讨ILE作为急性METH中毒解毒剂的潜在作用。
两组,每组六只雄性大鼠,腹腔注射METH(45mg/kg)。5至7分钟后,通过尾静脉给予18.6ml/kg 20%的ILE或生理盐水(NS)。在给予METH后的不同时间评估运动和行为活动。还评估了体温和存活率。然后取出脑和内脏进行组织学检查和TUNEL检测。
ILE治疗大鼠METH中毒可预防大鼠死亡,并使METH诱导的体温过高恢复到正常水平(<0.05)。ILE减少了僵住和刻板行为,并增加了竖毛反应(<0.05)。运动活动也恢复到对照水平,尤其是在实验的最后几个小时。与对照组相比,给予ILE可降低肺部肺气肿的发生率(<0.05和P<0.01)以及脑中TUNEL阳性细胞的百分比(<0.05)。
ILE可降低METH诱导的动物毒性严重程度以及死亡率。静脉输注脂质乳剂可能挽救对标准初始治疗无反应的急性METH中毒患者的生命。