许羚, 胡玥, 丁晓霜, 周谡, 唐黎明, 石劲敏. 雷公藤红素体内与体外急性毒性试验结果的比较[J]. 环境与职业医学, 2015, 32(6): 535-538,548. DOI: 10.13213/j.cnki.jeom.2015.15201
引用本文: 许羚, 胡玥, 丁晓霜, 周谡, 唐黎明, 石劲敏. 雷公藤红素体内与体外急性毒性试验结果的比较[J]. 环境与职业医学, 2015, 32(6): 535-538,548. DOI: 10.13213/j.cnki.jeom.2015.15201
XU Ling , HU Yue , DING Xiao-shuang , ZHOU Su , TANG Li-ming , SHI Jing-min . Comparison on Acute Toxicity of Celastrol Derived from in vivo and in vitro Methods[J]. Journal of Environmental and Occupational Medicine, 2015, 32(6): 535-538,548. DOI: 10.13213/j.cnki.jeom.2015.15201
Citation: XU Ling , HU Yue , DING Xiao-shuang , ZHOU Su , TANG Li-ming , SHI Jing-min . Comparison on Acute Toxicity of Celastrol Derived from in vivo and in vitro Methods[J]. Journal of Environmental and Occupational Medicine, 2015, 32(6): 535-538,548. DOI: 10.13213/j.cnki.jeom.2015.15201

雷公藤红素体内与体外急性毒性试验结果的比较

Comparison on Acute Toxicity of Celastrol Derived from in vivo and in vitro Methods

  • 摘要: 目的 研究雷公藤红素对3T3细胞的毒性作用,获得的细胞毒性结果预测急性毒性半数致死量(LD50),并与采用小鼠上下法(UDP)和Bliss法测定的急性毒性数值进行比较。

    方法 以已验证的3T3细胞中性红摄取为细胞毒性模型,以0.01~2.05 mg/L的8个浓度(剂间比为2.15)的雷公藤红素进行处理,分别于处理后48 h进行中性红摄取试验,计算半数抑制浓度(IC50)。以RC数学模型预测其全身急性毒性LD50。参考此LD50值设定起始剂量进行小鼠上下法实验。取70只ICR小鼠,雌雄各半,以3、4、5、6、7、8 mg/kg的雷公藤红素溶液和0 mg/kg4%二甲亚砜(DMSO)氯化钠注射液静脉给药,观察14 d,根据动物死亡率采用Bliss法计算LD50

    结果 雷公藤红素3T3细胞中性红摄取试验的IC50值为(0.1197& #177;0.0187)mg/L(n=2),决定系数R2> 0.96,预测其全身急性毒性LD50为5.375 mg/kg。上下法起始剂量设为3.3 mg/kg,测得雷公藤红素在ICR小鼠的LD50值为3.157 mg/kg, 95%可信区间为3.1~5.5 mg/kg。小鼠Bliss法测定急性毒性LD50为4.899 mg/kg, 95%可信区间为4.483~5.354 mg/kg。

    结论 雷公藤红素的体外3T3细胞毒性预测急性毒性与体内方法所得数值一致。

     

    Abstract: Objective To evaluate the cytotoxicity of celastrol on 3T3 cells, predict acute toxicity (LD50) based on the cytotoxicity data, and compare acute toxicity results by using mouse up-and-down method and Bliss method.

    Methods In this study, we employed an in-house validated in vitro cytotoxicity model based on the 3T3 cells neutral red uptake (NRU) assay. Using eight concentrations of celastrol (0.01-2.05 mg/L) for 48 h incubation, we calculated IC50 values for celastrol. The LD50 value of celastrol for systemic toxicity was computed by using RC model to set the starting dose for up-and-down procedure. Seventy ICR mice were divided into seven groups, half male and half female, and administered with 3, 4, 5, 6, 7, 8, and 0 mg/kg40% dimethyl sulfoxide (DMSO) and sodium chloride of celastrol intravenously. After observation for 14 days, we obtained LD50 values for celastrol using Bliss method based on the mortality rate.

    Results The IC50 values for celastrol using 3T3 cells NRU assay was (0.119 7& #177;0.018 7) mg/L (n=2), with coefficient of determination R2 > 0.96. The computed LD50 value for celastrol systemic toxicity was 5.375 mg/kg. The starting dose of up-and-down procedure was 3.3 mg/kg, and the derived LD50 value was 3.157 mg/kg with 95% confidence interval of 3.1-5.5 mg/kg. The LD50 value derived from Bliss method was 4.899 mg/kg with 95% confidence interval of 4.483-5.354 mg/kg.

    Conclusion The acute toxicity of celastrol predicted by 3T3 cytotoxicity test is consistent with the results by in vivo up-and-down procedure and Bliss method.

     

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