Quantification of aristolochic acid-derived DNA adducts in rat kidney and liver by using liquid chromatography–electrospray ionization mass spectrometry

Abstract

Aristolochic acid (AA), derived from the herbal genus Aristolochia and Asarum, has recently been shown to be associated with the development of nephropathy. Upon enzyme activation, AA is metabolized to the aristolactam-nitrenium ion intermediate, which reacts with the exocyclic amino group of the DNA bases via an electrophilic attack at its C7 position, leading to the formation of the corresponding DNA adducts. The AA-DNA adducts are believed to be associated with the nephrotoxic and carcinogenic effects of AA. In this study, liquid chromatography coupled with electrospray ionization mass spectrometry (LC–MS) was used to identify and quantify the AA–DNA adducts isolated from the kidney and liver tissues of the AA-dosed rats. The deoxycytidine adduct of AA (dC–AA) and the deoxyadenosine–AA adduct (dA–AA) were detected and quantified in the tissues of rats with one single oral dose (5 mg or 30 mg AA/kg body weight). The deoxyguanosine adduct (dG–AA), however, was detected only in the kidney of rats that were dosed at 30 mg AA/kg body weight for three consecutive days. The amount of AA–DNA adducts found in the rats correlated well with the dosage.