In this study, an in vitro nitric oxide (NO)-assay system based on the Griess reaction was used to investigate the (NO)-generating effects of aristolochic acid (AA) for the first time. AA was separated into its different components, aristolochic acid I (AAI) and aristolochic acid II (AAII), by preparative HPLC. AAI and AAII were incubated with human intestine bacteria (HIB) or rat intestine bacteria (RIB). A NO mixture generated from AAI and AAII by intestinal bacteria was observed and denitroso metabolites of AAI or AAII were detected in vitro by liquid chromatography/tandem mass spectrometry. Therefore, NO generation might be closely related to the metabolic process of AA in vitro. It suggested that one possible mechanism for the toxicity of AA may be due to the generation of NO from these compounds by intestinal bacteria.
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