Aristolochic acids （AAs）, a natural mixture of 8-methoxy-6-nitro-phenanthro-（3,4-d）-1,3-dioxolo-5-carboxylic acid （AAI）and 6-nitro-phenanthro-（3,4-d）-1,3-dioxolo-5-carboxylic acid （AAII）, derived from aristo...Aristolochic acids （AAs）, a natural mixture of 8-methoxy-6-nitro-phenanthro-（3,4-d）-1,3-dioxolo-5-carboxylic acid （AAI）and 6-nitro-phenanthro-（3,4-d）-1,3-dioxolo-5-carboxylic acid （AAII）, derived from aristolochiaceae species, has beenreported to cause AAS-induced nephropathy and upper urothelial cancer. In this review, we summarize the informationon the nephrotoxicity and carcinogenesis of AAs and their derivatives. AAs nephrotoxicity can lead to apoptosis andoxidative stress of renal tubular cells, and inhibition of the expression of aquaporins. AAs can also reduce the capabilityfor renal tubular epithelial cell repair after acute injury and further produce renal fibrosis by activating TGF-β-Smadsignaling and promoting the migration of macrophages. Moreover, AAs-induced carcinogenesis may be due to theformation of covalent adducts with DNA which can lead to the mutation in certain tumor suppressor genes orproto-oncogenes and the different catalyzing capacity of the microsomal cytochrome P450 of individuals in AAImetabolism.展开更多
文摘Aristolochic acids （AAs）, a natural mixture of 8-methoxy-6-nitro-phenanthro-（3,4-d）-1,3-dioxolo-5-carboxylic acid （AAI）and 6-nitro-phenanthro-（3,4-d）-1,3-dioxolo-5-carboxylic acid （AAII）, derived from aristolochiaceae species, has beenreported to cause AAS-induced nephropathy and upper urothelial cancer. In this review, we summarize the informationon the nephrotoxicity and carcinogenesis of AAs and their derivatives. AAs nephrotoxicity can lead to apoptosis andoxidative stress of renal tubular cells, and inhibition of the expression of aquaporins. AAs can also reduce the capabilityfor renal tubular epithelial cell repair after acute injury and further produce renal fibrosis by activating TGF-β-Smadsignaling and promoting the migration of macrophages. Moreover, AAs-induced carcinogenesis may be due to theformation of covalent adducts with DNA which can lead to the mutation in certain tumor suppressor genes orproto-oncogenes and the different catalyzing capacity of the microsomal cytochrome P450 of individuals in AAImetabolism.
