Cylindrospermopsin-induced metabolic reprogramming mapped in rat tissues by MALDI imaging

Area of Science:

• Toxicology
• Metabolomics
• Mass Spectrometry Imaging

Background:

• Cylindrospermopsin (CYN) is a cyanobacterial toxin known for liver and kidney damage.
• The spatial distribution and molecular effects of CYN in mammalian tissues are not fully understood.

Purpose of the Study:

• To investigate the spatial distribution and molecular effects of CYN in rat tissues.
• To assess CYN-induced lipid alterations in the stomach, liver, and kidneys using MALDI-MSI.
• To identify potential early molecular biomarkers of CYN exposure.

Main Methods:

• Oral exposure of rats to CYN (500 μg/kg).
• Analysis of stomach, liver, and kidney cryosections using matrix-assisted laser desorption/ionisation mass spectrometry imaging (MALDI-MSI).
• Lipidomic profiling and molecular annotation of detected metabolites.

Main Results:

• Spatially resolved ion images showed distinct tissue-specific lipid and metabolite distributions.
• Early CYN exposure in the stomach correlated with increased lysophosphatidylcholine and phosphatidylcholine species.
• The liver exhibited significant lipid remodelling, including elevated phosphatidylglycerols and polyunsaturated phosphatidylcholines, and decreased phosphatidylethanolamines and sulfatides.
• Kidney analysis suggested alterations in xenobiotic transport and detoxification pathways.

Conclusions:

• MALDI-MSI is effective for in situ investigation of toxin biodistribution and metabolic effects.
• CYN exposure induces organ-specific lipidomic responses in mammals.
• The study provides novel multi-organ spatial insights into early lipidomic changes induced by CYN, supporting the identification of potential biomarkers.