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普鲁士蓝和N-乙酰半胱氨酸对小鼠铊中毒的影响。

Effects of Prussian blue and N-acetylcysteine on thallium toxicity in mice.

作者信息

Meggs W J, Cahill-Morasco R, Shih R D, Goldfrank L R, Hoffman R S

机构信息

New York City Poison Control Center, USA.

出版信息

J Toxicol Clin Toxicol. 1997;35(2):163-6. doi: 10.3109/15563659709001187.

Abstract

BACKGROUND

Thallium poisoning is now rare but still occurs as a result of homicide attempts. Prussian blue's efficacy in the treatment of experimental thallium poisoning has been demonstrated in animal models, and its use in humans is supported by anecdotal data. Since thallium binds sulfhydryl groups, the use of N-acetylcysteine is also considered as a potential antidote.

STUDY OBJECTIVE

To compare the efficacy of Prussian blue and N-acetylcysteine in a murine model of thallium poisoning.

METHODS

Female Swiss albino mice with free access to food and water were used. Two study doses of thallium, given as a subcutaneous injection of thallium acetate dissolved in sterile water, were chosen: 70 mg/kg (LD90) and 85 mg/kg (> LD100). A randomized, placebo controlled study was conducted with survival at 120 h chosen as the outcome measure. Four treatment groups were studied: control, Prussian blue, N-acetylcysteine, and the combination of Prussian blue and N-acetylcysteine. Prussian blue was dissolved in water and given by oral gavage at a dose of 50 mg/kg. N-acetylcysteine was diluted in normal saline and given as intraperitoneal injections of 200 mg/kg. Sterile water by gavage and normal saline by peritoneal injection were given as control treatments whenever an active agent was not given. Survival was recorded over a 120 h study period and compared at 120 h by a Fisher's exact test.

RESULTS

At 120 h following subcutaneous injection of thallium 70 mg/kg, only 10% of the control animals survived. Treatment with N-acetylcysteine or Prussian blue increased survival to 35% (p = 0.13) and 50% (p = 0.014), respectively. The addition of N-acetylcysteine to Prussian blue offered no benefit over Prussian blue therapy alone.

CONCLUSIONS

Prussian blue was found to decrease mortality from thallium poisoning at a dose equal to the LD90 in this model, but not a dose greater than the LD100. No role for N-acetylcysteine in the treatment of thallium poisoning was demonstrated by this study.

摘要

背景

铊中毒如今已较为罕见,但仍会因蓄意谋杀而发生。普鲁士蓝在实验性铊中毒治疗中的疗效已在动物模型中得到证实,其在人体中的应用也有轶事性数据支持。由于铊会结合巯基,N - 乙酰半胱氨酸的使用也被视为一种潜在的解毒剂。

研究目的

在铊中毒的小鼠模型中比较普鲁士蓝和N - 乙酰半胱氨酸的疗效。

方法

使用可自由获取食物和水的雌性瑞士白化小鼠。选择两种研究剂量的铊,以皮下注射溶解于无菌水中的醋酸铊的方式给药:70 mg/kg(LD90)和85 mg/kg(> LD100)。进行了一项随机、安慰剂对照研究,将120小时的生存率作为结局指标。研究了四个治疗组:对照组、普鲁士蓝组、N - 乙酰半胱氨酸组以及普鲁士蓝与N - 乙酰半胱氨酸联合组。普鲁士蓝溶解于水中,以50 mg/kg的剂量经口灌胃给药。N - 乙酰半胱氨酸用生理盐水稀释,以200 mg/kg的剂量腹腔注射给药。每当未给予活性剂时,分别经口灌胃给予无菌水和腹腔注射生理盐水作为对照治疗。在120小时的研究期间记录生存率,并在120小时时通过Fisher精确检验进行比较。

结果

皮下注射70 mg/kg铊后120小时,对照组动物仅有10%存活。用N - 乙酰半胱氨酸或普鲁士蓝治疗后,生存率分别提高到35%(p = 0.13)和50%(p = 0.014)。在普鲁士蓝治疗基础上加用N - 乙酰半胱氨酸并不比单独使用普鲁士蓝治疗更具优势。

结论

在该模型中,发现普鲁士蓝以等于LD90的剂量可降低铊中毒死亡率,但高于LD100的剂量则不能。本研究未证明N - 乙酰半胱氨酸在铊中毒治疗中有作用。

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