Metabolic pathway and biological significance of glutathione detoxification of aristolochic acid Ⅰ

Abstract

Aristolochic acid I (AAI) is a nephrotoxic chemical found in the plant genera, Aristolochia and Asarum. AAI can be reduced to positively charged aristolochyl actam-nitrogen ions in organisms: this intermediate product increases the oxidative stress due to AAI. Glutathione (GSH) acts synergistically with other amino acids in the liver for metabolizing toxic chemicals. Further, this small peptide containing an -SH group binds to AAI and reduces oxidative stress in A549 cells exposed to AAI. Surface-enhanced Raman scattering (SERS) was selected to explore the metabolites of the reaction between AAI and GSH. Ag@HSA was used as the basis for detecting metabolites based on its excellent biocompatibility. Moreover, scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersive X-ray spectroscopy (EDX), and dynamic light scattering (DLS) were used to characterize the prepared SERS support substrate. A luminescence experiment was used to detect metabolites based on their chemical characteristics. In vivo tests in nude mice showed that AAI displays high toxicity. An injection of 200 μL AAI (10−4 M) into the abdominal cavity caused rapid death. CCK-8 assays showed that the viability of cells increased after adding GSH, indicating that GSH is involved in the detoxification metabolism of AAI.

Keywords

• AAI
• CCK-8 assay
• Nude mice
• Laser confocal
• SERS