揭示鸦片碱与肝癌的相关性：时空异质性现象
Unveiling correlations between aristolochic acids and liver cancer: spatiotemporal heterogeneity phenomenon
DOI 原文链接
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影响因子:5.7
分区:医学2区 / 全科医学与补充医学2区 药学2区
发表日期:2024 Sep 28
作者:
Chengxian Li, Xinyu Li, Ming Niu, Dake Xiao, Ye Luo, Yinkang Wang, Zhi-E Fang, Xiaoyan Zhan, Xu Zhao, Mingxia Fang, Jiabo Wang, Xiaohe Xiao, Zhaofang Bai
DOI:
10.1186/s13020-024-01003-y
摘要
鸦片碱是一类存在于归附科植物中的天然化合物，具有相似的结构骨架和化学性质。暴露于鸦片碱是严重肾脏疾病和泌尿系统癌症的风险因素。然而，鸦片碱对肝脏（作为其主要代谢部位）致癌性的研究尚不充分。尽管在肝脏中检测到鸦片碱诱导的突变特征指纹，且已知其具有肝毒性，但鸦片碱是否能直接引起肝癌尚未得到验证。本文总结了鸦片碱在动物实验中的长期致癌性研究结果，提出其致癌性存在时空异质性，可能解释为何在成人中尚未发现鸦片碱直接引起肝癌的确凿证据。我们还综述了减缓鸦片碱引起的肝毒性的方法，旨在应对相关的全球安全问题，并为未来的研究提供方向和建议。
Abstract
Aristolochic acids are a class of naturally occurring compounds in Aristolochiaceae that have similar structural skeletons and chemical properties. Exposure to aristolochic acids is a risk factor for severe kidney disease and urinary system cancer. However, the carcinogenicity of aristolochic acids to the liver, which is the main site of aristolochic acid metabolism, is unclear. Although the characteristic fingerprint of aristolochic acid-induced mutations has been detected in the liver and aristolochic acids are known to be hepatotoxic, whether aristolochic acids can directly cause liver cancer is yet to be verified. This review summarizes the findings of long-term carcinogenicity studies of aristolochic acids in experimental animals. We propose that spatiotemporal heterogeneity in the carcinogenicity of these phytochemicals could explain why direct evidence of aristolochic acids causing liver cancer has never been found in adult individuals. We also summarized the reported approaches to mitigate aristolochic acid-induced hepatotoxicity to better address the associated global safety issue and provide directions and recommendations for future investigation.