Visualization of the distribution of anthraquinone components from madder roots in rat kidneys by desorption electrospray ionization-time-of-flight mass spectrometry imaging

Madder color (MC), a natural dye isolated from Rubia tinctorum, is a potent carcinogen that targets the outer stripe of outer medulla (OSOM) in the kidneys of rats. To clarify the role of MC components in renal carcinogenesis, we examined distributions of MC components and metabolites in the kidneys of rats treated with MC using desorption electrospray ionization-mass spectrometry imaging (DESI-MSI). Alizarin, lucidin, munjistin, nordamnacanthal, purpurin, pseudopurpurin, rubiadin, and some other metabolites detected and identified by liquid chromatography time-of-flight MS analysis of rat serum 1 h after MC administration were subjected to DESI-MSI. This analysis enabled visualization of the distribution of anthraquinones in the kidney, and the ion images showed a characteristic distribution according to their chemical structure. Among the components, lucidin and rubiadin specifically localized in the OSOM, suggesting that their genotoxicity was a direct cause of MC carcinogenesis. Alizarin showed greater distribution in the OSOM than the cortex and may therefore participate in renal carcinogenicity owing to its tumor-promoting activity. Overall, our data suggested that the distribution of carcinogenic components to the OSOM was responsible for the site-specific renal carcinogenicity of MC and that DESI-MSI analysis may be a powerful tool for exploring the mechanisms of chemical carcinogenesis.