Acute and sub-chronic oral toxicity profiles of the aqueous extract of Cortex Dictamni in mice and rats
Acute and sub-chronic oral toxicity profiles of the aqueous extract of Cortex Dictamni in mice and rats
复制标题
DOI：
10.1016/j.jep.2014.10.027
复制
发表时间：
2014-12-02
影响因子：
5.4
通讯作者：
Xu, Yang
中科院分区：
文献类型：
--
作者：
Wang, Lili;Li, Zhiqiang;Xu, Yang
民族药理学相关性：地皮在中国民间医学中用于治疗黄疸、咳嗽、风湿病和一些皮肤病；然而，其可能的毒性尚未得到严格的研究。本研究通过急性和亚慢性毒性研究来评价地皮水提取物（CDAE）的安全性。材料与方法：在急性毒性试验中，7组小鼠（n=5/组/性别）分别口服剂量为0、28.7、33.6、39.7、46.7、54.9和64.6 g/kg的CDAE，记录其一般行为、不良反应和死亡率，持续14 d。在亚慢性毒性试验中，动物以0、3.0、6.0或12.0 g/kg/天（n=10/组/性别）的剂量灌胃CDAE，持续4周，然后进行2周的恢复期。测定小鼠的生化、血液学和形态学参数。结果：在成年小鼠中，单次口服CDAE （0-64.6 g/kg体重）可导致一般行为不良反应的发生率增加。死亡率也随着剂量的增加而增加（LD50=48.2 g/kg）。在大鼠中，每日单次口服剂量的CDAE在4周后行为耐受良好，并且没有引起体重的显著变化。然而，在给药和恢复期结束时，肝脏的绝对重量和相对重量都显著升高，尽管各器官的组织学检查显示对照组和治疗组之间没有差异。血液学和生化指标发生显著变化；淋巴细胞、丙氨酸转氨酶、碱性磷酸酶水平显著降低，中性粒细胞、白蛋白、总胆固醇、葡萄糖和尿素氮水平显著升高，提示造血功能和肝肾功能紊乱。结论：总的来说，CDAE的急性毒性没有明显的观察到。然而，考虑到亚慢性口服毒性研究中某些血液学和肝功能参数以及肝体重比的变化，CDAE可能具有选择性毒性。2014爱思唯尔爱尔兰有限公司版权所有。
Ethnopharmacological relevance: Cortex Dictamni is used in Chinese folk medicine for the treatment of jaundice, cough, rheumatism and some skin diseases; however, its possible toxicity has not been rigorously studied. The present investigation was carried out to evaluate the safety of Cortex Dictamni aqueous extract (CDAE) by acute and sub-chronic toxicity studies.Materials and methods: In acute toxicity tests, seven groups of mice (n=5/group/sex) were orally treated with doses of 0, 28.7, 33.6, 39.7, 46.7, 54.9 and 64.6 g/kg of CDAE and general behavior, adverse effects and mortality were recorded for up to 14 days. In sub-chronic toxicity assays, animals received CDAE by gavage at the doses of 0, 3.0, 6.0 or 12.0 g/kg/day (n=10/group/sex) for 4 weeks and then followed for a 2-week recovery period. The biochemical, hematological and morphological parameters were determined.Results: In adult mice, single oral administrations of CDAE (0-64.6 g/kg body weight) induced an increase in the incidence of general behavioral adverse effects. The mortality rate also increased with increasing dosage (LD50=48.2 g/kg). In rats, daily single oral doses of CDAE were well tolerated behaviorally after 4 weeks and induced no significant changes in body weights. However, the absolute and relative liver weight at the end of both administration and recovery periods were significantly elevated, although the histological examination of various organs revealed no differences between the control and the treated groups. The hematological and biochemical parameters were significantly changed; lymphocytes, alanine transaminase, alkaline phosphatase levels showed a significant decrease while neutrophilic granulocyte, albumin, total cholesterol, glucose and blood urea nitrogen levels showed a significant increase, suggesting disturbances of hematopoiesis and liver and kidney functions.Conclusions: Overall, the acute toxicity of CDAE was not clearly observed. However, it is possible that CDAE has a selective toxicity considering the changes in some hematological and liver function parameters and the liver-body weight ratios in the sub-chronic oral toxicity study. (C) 2014 Elsevier Ireland Ltd. All rights reserved.