Nephrotoxicity and carcinogenesis of aristolochic acids and their derivates

Aristolochic acids (AAs), a natural mixture of 8methoxy6nitrophenanthro(3,4d)1,3dioxolo5carboxylic acid (AAI) and 6nitrophenanthro(3,4d)1,3dioxolo5carboxylic acid (AAⅡ, derived from aristolochiaceae species, has been reported to cause AASinduced nephropathy and upper urothelial cancer. In this review, we summarize the information on the nephrotoxicity and carcinogenesis of AAs and their derivatives. AAs nephrotoxicity can lead to apoptosis and oxidative stress of renal tubular cells, and inhibition of the expression of aquaporins. AAs can also reduce the capability for renal tubular epithelial cell repair after acute injury and further produce renal fibrosis by activating TGFβSmad signaling and promoting the migration of macrophages. Moreover, AAsinduced carcinogenesis may be due to the formation of covalent adducts with DNA which can lead to the mutation in certain tumor suppressor genes or protooncogenes and the different catalyzing capacity of the microsomal cytochrome P450 of individuals in AAI metabolism.