Cyanotoxins induce hepatic inflammation and disrupt lipid metabolism in Sinocyclocheilus grahami.

Cyanobacterial blooms release a variety of secondary metabolites, severely impacting the survival of fish species.The multi-layered analytical approach (histology + biochemistry + transcriptomics + lipidomics) was used to investigate hepatic injury in Sinocyclocheilus grahami following a 96-hour exposure to Microcystis aeruginosa exudates (MaE) and their constituent, phytosphingosine (PHS; at 2.9 and 145 ng/mL). The results showed histopathological hepatic damage across treatments, with a significantly decreased hepatosomatic index (HSI) in the high-PHS-exposure group. Total bilirubin were significantly elevated in all treatments. Interestingly, the triglyceride content showed significant increases in the PHS-treated groups. Both MaE and PHS induced inflammation, with significantly up-regulated inflammatory factors, whereas the anti-inflammatory factor IL-10 was significantly down-regulated in the MaE-treated group. Based on biochemical biomarker and multi-omics analyses, MaE mainly induced oxidative stress and lipid peroxidation, whereas PHS tended more to disturb lipid metabolism, markedly down-regulating various metabolites in the liver. In the PHS-treated groups, sphingolipid and retinol metabolisms emerged as the top two most enriched KEGG pathways with the largest number of DEGs and DEMs. In conclusion, the toxicological differences induced by MaE and PHS mainly depended on their chemical property. (1) As a pure sphingolipid compound, the biological processes of PHS were enriched in metabolic processes, its cellular component processes were enriched in the endoplasmic reticulum, the site of sphingomyelin synthesis, and its molecular function processes involved binding with DNAs associated with PPAR and FoxO signaling pathways. (2) As a complex mixture of exudates, MaE mainly triggered responses to toxicins/extracellular stimuli and lipid transporter activity. MaE exerted strong oxidative stress, while PHS tended more to disturb lipid metabolism, and both induced inflammation. This study contributes to the health risk assessment of fish in the context of cyanobacterial blooms.