马兜铃酸细胞分子毒理学研究进展

马兜铃酸属于硝基菲类化合物,广泛存在于马兜铃属中药中,具有肾毒性和潜在的致癌作用。马兜铃酸诱导肾小管上皮细胞纤维化及凋亡;促进细胞周期加速,而导致泌尿道上皮异常增殖;经还原代谢,并与DNA形成加合物,使ras基因和p53基因突变,进而诱发癌变。本文对马兜铃酸的细胞分子毒性机制进行了综述,并对可能的减毒方法进行了探讨。

Molecular cellular toxicology of aristolochic acid and its advances

Aristolochic acid is a nitrophenanthrene derivative isolated from most of Aristolochia species and has been shown to be a nephrotoxicity and a potent carcinogen to both rats and human. Aristolochic acid induced transdifferentiation and apoptosis in human tubular epithelial cells, and induced proliferation anormally through cell cycle progression, and induced mutation in the ras and p53 genes by DNA adduct formation via reductive metabolism, and then induced cancer. In this paper, the underlying cellular and molecular mechanisms of toxicity of aristolochic acid and methods of attenuation are elucidated.