Toxicological Studies of Daphnetin
Toxicological Studies of Daphnetin
复制标题
瑞香素的毒理学研究
DOI：
10.4103/pm.pm_523_17
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发表时间：
2018-10-01
影响因子：
0.7
通讯作者：
Fu Yingyuan
中科院分区：
文献类型：
--
作者：
Kuang Nanzhen;Wang Jieying;Fu Yingyuan
背景资料：大量研究表明，瑞香素（DAP）具有抗炎、抗氧化、抗菌、抗肿瘤、抗关节炎等广泛的药理作用。然而，其遗传毒性很少被检查。材料与方法：采用鼠伤寒沙门氏菌/哺乳动物微粒体酶试验（艾姆斯试验）、骨髓微核试验、急性皮肤过敏试验和局部粘膜刺激试验，通过急性毒性试验评价DAP的安全性。结果如下：小鼠灌胃给药剂量为100 mg/kg体重，超过全身有效剂量的175倍，连续观察14 d，小鼠未出现中毒症状。在艾姆斯试验中，每个剂量的DAP导致回复突变菌落数< 2，是阴性对照组突变菌落数的两倍，表明结果为阴性。DAP各剂量组微核率与阴性对照组比较差异无统计学意义（P > 0.05），与环磷酰胺阳性对照组比较差异有统计学意义（P < 0.05）。家兔皮肤对DAP或10%二甲基亚砜（DMSO）无刺激反应，包括无红斑、水肿或致敏现象。家兔口腔粘膜给予DAP后，一般情况良好，未观察到口腔粘膜红斑、糜烂、溃疡或其他刺激反应。结论：在试验剂量范围内，DAP未引起任何观察到的毒性效应、致突变效应、致敏或刺激。
Background: Numerous studies have demonstrated that daphnetin (DAP) has anti-inflammatory, antioxidant, antibacterial, antitumor, anti-arthritic, and other extensive pharmacological effects. However, its genotoxicity has rarely been examined. Materials and Methods: The safety of DAP was evaluated by an acute toxicity test using a Salmonella typhimurium/mammalian microsomal enzyme assay (Ames test), bone marrow micronucleus test, acute skin allergy test, and local mucosal irritation test. Results: Mice received a dose of 100 mg/kg body weight through lavage, which is more than 175 times the whole-body effective dose and were continuously observed for 14 d; mice showed no signs of poisoning. In the Ames test, each dose of DAP resulted in numbers of revertant colonies that were < 2 two times the number of mutation colonies in the negative control group, indicating a negative result. The micronucleus rate of each DAP dose group was not significantly different from that of the negative control group (P > 0.05) but was significantly different from that of the cyclophosphamide (CTX)-positive control group (P < 0.05). Rabbit skin showed no stimulation reaction to DAP or 10% dimethyl sulfoxide (DMSO), including no erythema, edema, or sensitization phenomena. Rabbits were generally in good condition after dosing the oral mucosa with DAP, and no oral mucosal erythema, erosion, ulcers, or other irritation reactions were observed. Conclusions: Within the range of tested doses, DAP did not cause any observed toxic effects, mutagenic effects, sensitization, or stimulation.