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

Cylindrospermopsin (CYN) is a cyanobacterial toxin with hepatotoxic and nephrotoxic properties; however, its spatial distribution and molecular effects in mammalian tissues remain unclear. In this study, matrix-assisted laser desorption/ionisation mass spectrometry imaging (MALDI-MSI) was employed to assess toxin-induced lipid alterations in the stomach, liver, and kidneys of rats orally exposed to 500 μg CYN/kg body weight and euthanised at 0, 2, 4, 6, and 24 h. Cryosections were analysed under optimised conditions for CYN detection, followed by molecular annotation and lipidomic profiling. Spatially resolved ion images revealed distinct lipid and metabolite distributions and tissue-specific metabolic responses. The transient detection of CYN and its adducts in the stomach during early exposure coincided with increased lysophosphatidylcholine and phosphatidylcholine species, suggesting membrane remodelling. The liver exhibited pronounced lipid remodelling, with elevated phosphatidylglycerols and polyunsaturated phosphatidylcholines and decreased phosphatidylethanolamines and sulfatides, consistent with potential mitochondrial dysfunction and inflammatory involvement. In the kidney, detection of CYN by ultra-high performance liquid chromatography-tandem mass spectrometry and spatial accumulation patterns suggested alterations in xenobiotic transport and detoxification. These findings suggest organ-specific lipidomic responses possibly associated with CYN and highlight the utility of MALDI-MSI for in situ investigation of toxin biodistribution and metabolic effects. They provide novel multi-organ spatial insights into early lipidomic changes induced by CYN and support the identification of potential early molecular biomarkers of exposure.