马兜铃酸是马兜铃科植物中天然存在的一类化合物，具有相似的结构骨架和化学性质。接触马兜铃酸是严重肾脏疾病和泌尿系统癌症的危险因素。然而，马兜铃酸对肝脏（马兜铃酸代谢的主要场所）的致癌性尚不清楚。尽管在肝脏中检测到了马兜铃酸诱导突变的特征指纹，并且已知马兜铃酸具有肝毒性，但马兜铃酸是否可以直接导致肝癌仍有待验证。本综述总结了马兜铃酸在实验动物中的长期致癌性研究的结果。我们提出，这些植物化学物质致癌性的时空异质性可以解释为什么在成人个体中从未发现马兜铃酸导致肝癌的直接证据。我们还总结了已报道的减轻马兜铃酸引起的肝毒性的方法，以更好地解决相关的全球安全问题，并为未来的研究提供方向和建议。© 2024。作者。

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.© 2024. The Author(s).