New Dual-Spectroscopic Strategy for the Direct Detection of Aristolochic Acids in Blood and Tissue.

Abstract

Aristolochic acids (AAs) contained in herbal plants are implicated in multiple organ injuries and have a high mutational burden in upper tract urothelial cancers. The currently available techniques for monitoring AAs include LC (liquid chromatography) and LC/MS (mass spectrometry), but the application of these approaches are limited due to the complex sample preparation and derivatization steps. Therefore, there is an urgent need to develop efficient methods for identifying and quantifying AAs. Here, we present a new dual-spectroscopic approach for the direct detection of AAs from blood and tissue samples; the detection of aristolochic acid I (AAI) is performed by surface-enhanced Raman spectroscopy (SERS), and its bioproduct, aristololactam (AAT), is detected by fluorescence spectroscopy based on their distinctive spectral response. Furthermore, a graphene assisted enrichment coupled with a magnetic retrieval strategy was developed to enhance SERS sensitivity toward AAI. Our method was successfully applied to directly determine both AAI and AAT from the blood, liver, and kidney of rats. The potential for real-world application was demonstrated by continuously monitoring AAI and AAT in rat blood and tissues after AAI feeding. The results showed that AAI was gradually metabolized to AAT and transported to different organs. It was found that the metabolism of AAI took place in the kidney, but AAT residue was detected in both liver and kidney, which might be related to long-term toxicity and gene mutation. The proposed dual-spectroscopic strategy is applicable to long-term toxicology research and to the direct diagnosis of AAI-induced organ injury.