Vitamin K is involved in liver protection and repair: Mitigating hepatotoxicity induced by the nitrite environment in grass carp (Ctenopharyngodon idella) by modulating Golgi function, hepatic stellate cells and mitochondrial dynamics

Nitrite is a toxic substance widely present in aquaculture water environments. This study explored the impact of vitamin K on liver pathology in grass carp ( Ctenopharyngodon idella ) challenged with nitrite. Grass carp received diets with six vitamin K concentrations (0 + sulfamethoxazole, 0, 1, 2, 3, and 4 mg/kg) for 60 days, then endured a 96-h nitrite stress test. Our results showed that vitamin K enhanced growth performance and reduced damage indicators in adult grass carp, including weight gain percentage (PWG), glutamic-pyruvic transaminase (GPT), and methemoglobin (MetHB). At the cellular level, vitamin K upregulated the expression of Golgi apparatus matrix protein 130 (GM130) and acid sphingomyelinase (ASM) in hepatocytes, increased sphingomyelin and ceramides levels, and repaired stress-damaged cell membranes. At the tissue level, vitamin K promoted liver regeneration by upregulating repair markers α-smooth muscle actin (α-SMA) and transforming growth factor-β (TGF-β) and boosting collagen deposition via growth arrest-specific 6 (GAS6) and its receptor AXL. Additionally, vitamin K alleviated nitrite-induced hepatocyte apoptosis, potentially through upregulating the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway to maintain mitochondrial homeostasis. With PWG and GPT as indicators, the optimal vitamin K requirements for normal and nitrite resistance of adult grass carp were 1.88 and 1.94 mg/kg, respectively. This study assessed the effects of nitrite exposure on grass carp liver, elucidated the potential mechanism by which vitamin K mitigates such damage, and provided novel insights for alleviating nitrite stress in fish.