Journal article
Mapping insoluble indole metabolites in the gastrointestinal environment of a murine colorectal cancer model using desorption/ionisation on porous silicon imaging
Scientific Reports, Vol.9, pp.1-13
2019
PMID: 31451756
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Source: InCites
Abstract
Indole derivatives are a structurally diverse group of compounds found in food, toxins, medicines, and produced by commensal microbiota. On contact with acidic stomach conditions, indoles undergo condensation to generate metabolites that vary in solubility, activity and toxicity as they move through the gut. Here, using halogenated ions, we map promising chemo-preventative indoles, i) 6-bromoisatin (6Br), ii) the mixed indole natural extract (NE) 6Br is found in, and iii) the highly insoluble metabolites formed in vivo using desorption/ionisation on porous silicon-mass spectrometry imaging (DIOS-MSI). The functionalised porous silicon architecture allowed insoluble metabolites to be detected that would otherwise evade most analytical platforms, providing direct evidence for identifying the therapeutic component, 6Br, from the mixed indole NE. As a therapeutic lead, 0.025 mg/g 6Br acts as a chemo-preventative compound in a 12 week genotoxic mouse model; at this dose 6Br significantly reduces epithelial cell proliferation, tumour precursors (aberrant crypt foci; ACF); and tumour numbers while having minimal effects on liver, blood biochemistry and weight parameters compared to controls. The same could not be said for the NE where 6Br originates, which significantly increased liver damage markers. DIOS-MSI revealed a large range of previously unknown insoluble metabolites that could contribute to reduced efficacy and increased toxicity.
Details
- Title
- Mapping insoluble indole metabolites in the gastrointestinal environment of a murine colorectal cancer model using desorption/ionisation on porous silicon imaging
- Creators
- David Andre Rudd - Southern Cross UniversityKirsten Benkendorff - Southern Cross UniversityCharndeep Chahal - Flinders UniversityTaryn Guinan - Melbourne Centre for NanofabricationOve Johan Ragnar Gustafsson - University of South AustraliaBabak Esmaeelian - Flinders UniversityHanna Krysinska - Flinders UniversityLisa Pogson - Flinders UniversityNicolas Hans Voelcker - Melbourne Centre for NanofabricationCatherine Anne Abbott - Flinders University
- Publication Details
- Scientific Reports, Vol.9, pp.1-13
- Publisher
- Nature Publishing Group UK; London
- Identifiers
- 991012849400202368
- Academic Unit
- Faculty of Science and Engineering; Marine Ecology Research Centre; School of Environment, Science and Engineering; Science
- Language
- English
- Resource Type
- Journal article