Guo Peng-Jie, Lin Zhi-Jian, Zhang Xiao-Meng, Zou Li-Na, Guo Fan-Fan, Zhang Bing
School of Chinese Materia Medica, Beijing University of Chinese Medicine Beijing 100029, China.
Zhongguo Zhong Yao Za Zhi. 2020 Feb;45(3):518-522. doi: 10.19540/j.cnki.cjcmm.20190827.401.
Coumarin is an important class of natural organic compounds, which widely exists in a variety of plants and microorganisms. Coumarins have many biological activities and wide clinical applications, such as anti-tumor, anti-HIV, anti-bacterial, anti-inflammatory, anti-oxidation, anti-coagulation, but they have obvious toxic effects in rodents. It was found that the toxicity of coumarins in different animals and organs was significantly different, and high dose oral administration was more likely to produce toxic reactions. Based on the research and analysis of domestic and foreign literatures in recent 60 years, this paper mainly summarized the hepatotoxicity and pulmonary toxicity induced by coumarins, and probed into their possible mechanisms. It was found that the toxicity of coumarins had metabolic differences and species differences. The liver of rats and lungs of mice were more susceptible to coumarins. Toxic reactions occurred mainly in the second metabolic pathway of coumarin metabolism in vivo. In order to put forward safety considerations and evaluate the impact of coumarin on human body, it was found that coumarin is unlikely to produce hepatotoxicity at normal exposure level. It was also suggested that species differences due to different metabolic patterns in model animals should be carefully considered when assessing coumarin toxicity, in order to provide reference for clinical research and rational use of coumarins and improve the rational use of coumarins.
香豆素是一类重要的天然有机化合物，广泛存在于多种植物和微生物中。香豆素具有多种生物活性和广泛的临床应用，如抗肿瘤、抗艾滋病毒、抗菌、抗炎、抗氧化、抗凝血等，但它们在啮齿动物中具有明显的毒性作用。研究发现，香豆素在不同动物和器官中的毒性存在显著差异，高剂量口服给药更易产生毒性反应。基于近60年国内外文献的研究分析，本文主要总结了香豆素引起的肝毒性和肺毒性，并探讨了其可能的机制。研究发现，香豆素的毒性存在代谢差异和种属差异。大鼠的肝脏和小鼠的肺对香豆素更为敏感。毒性反应主要发生在香豆素体内代谢的第二条途径中。为了提出安全性考量并评估香豆素对人体的影响，研究发现香豆素在正常暴露水平下不太可能产生肝毒性。还建议在评估香豆素毒性时应仔细考虑模型动物因代谢模式不同而产生的种属差异，以便为香豆素的临床研究和合理使用提供参考，提高香豆素的合理使用水平。
