Neuroendocrine-mediated hepatopancreatic immunosuppression and metabolic reprogramming in Eriocheir sinensis under nitrite stress

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Nitrite is a prevalent pollutant in global aquaculture systems that causes mass mortality in crustaceans through multisystem dysfunction. This study evaluated hepatopancreatic responses of Eriocheir sinensis to nitrite exposure (0, 2.5, 5, 10, and 20 mg/L) for 48 h, integrating histopathological, immunological, metabolic, and neuroendocrine analyses. Nitrite triggered dose-dependent biphasic regulation: haemolymph dopamine (DA) and crustacean hyperglycemic hormone (CHH) increased at low nitrite concentrations (2.5–5 mg/L) but decreased significantly at 20 mg/L, perturbing cAMP/cGMP/DAG second messengers and PKA/PKG/PKC kinases. The AMPK/CREB axis was activated at 5–10 mg/L but inhibited at 20 mg/L nitrite. Immune-antioxidant responses included reduced haemolymph hemocyanin, elevated hepatopancreatic malondialdehyde (MDA) (10–20 mg/L), suppressed SOD, CAT, PO, and LZM (20 mg/L), and transient ACP/AKP (peaking at 2.5–5 mg/L). Transcriptional-level analysis revealed that hsp90 , lzm , alf3 , and crustin were upregulated at 5 mg/L but downregulated at 20 mg/L. Metabolically, glycolysis enzymes (HK, PK) and genes ( glut1 , hk , g6p ) were upregulated at 5–10 mg/L but suppressed at 20 mg/L, while lipid metabolism markers (FAS, CACT, pparγ , elovl6 , fabp1 , dgat1 ) revealed suppressed lipogenesis and enhanced fatty acid β-oxidation. These changes correlated with hyperglycemia-lactic acidosis, hypolipidemia, and decreased glycogen/ATP reserves. Partial least squares path modeling (PLS-PM) identified DA as the dominant regulator bridging neuroendocrine disruption to metabolic collapse. Our findings elucidate the integrated toxic mechanisms of nitrite in E. sinensis , providing critical insights for targeted health management in crab aquaculture.