Multi-omics analysis reveals hepatic lipid metabolic disruption and oxidative stress in Pelodiscus sinensis after microcystin-LR exposure

Microcystins (MCs) are a major class of hepatotoxins that significantly threaten aquatic ecosystems and aquaculture. This study systematically examined the toxic effects and molecular mechanisms in the freshwater turtle Pelodiscus sinensis, an economically important species, following acute (24 h) exposure to different concentrations of microcystin-LR (MC-LR). Results revealed dose-dependent alterations in hepatic antioxidant capacity, with significant increases in T-AOC, GPx, and GST activities. Besides, the MDA content was increased by 58.82% at 71 μg/kg bw, indicating lipid peroxidation. Serum biochemical analyses revealed dynamic alterations, featuring significant elevations in TC and LDL-c, accompanied by a concurrent decline in HDL-c. Besides, histopathological examination demonstrated MC-LR-induced hepatocellular damage characterized by inflammatory infiltration, vacuolization, and structural disorganization. Comparative transcriptomic analysis revealed significant alterations in pathways related to mitophagy, apoptosis, ferroptosis, and lipid metabolism, with weighted gene co-expression network analysis (WGCNA) highlighting AOAH, LCP1, NUP88, and NUAK2 as hub genes linked to lipid metabolism and oxidative stress. Complementary lipidomic analysis uncovered disturbances in glycerophospholipid and glycerolipid metabolism, where ceramides (Cers) and triacylglycerols (TGs) may serve as hub lipids. Collectively, these findings demonstrated that MC-LR exposure induced substantial physiological disruptions in P. sinensis, especially in lipid and antioxidant metabolisms, which provided novel mechanistic insights into MC-LR toxicity in P. sinensis.