Probiotics Alleviate Nonylphenol-Induced Hepatotoxicity in Silurus meridionalis via Reprogramming Arachidonic Acid Metabolism and Suppressing Ferroptosis: A Preliminary Study

Nonylphenol (NP), a typical emerging pollutant, is widely detected in water bodies, yet its hepatotoxic mechanisms and mitigation strategies remain underexplored. This study evaluated the protective effects of a mixed probiotic (Lactobacillus acidophilus and Bacillus subtilis) against NP-induced hepatotoxicity in Silurus meridionalis by integrating transcriptomic and metabolomic analyses, with validation by RT-qPCR and ELISA. The results showed that NP exposure disrupted the arachidonic acid (AA) pathway (activating pro-inflammatory COX and LOX pathways while the suppressing anti-inflammatory CYP450 branch), promoted ferroptosis via iron dyshomeostasis and oxidative damage, and impaired triglyceride (TG) synthesis. Probiotic pretreatment reversed these toxic effects by modulating AA metabolism, suppressing COX (ptgs2a↓ → PGE2↓) and LOX (alox12↓ → MDA↓) pathways, while upregulating the CYP450 pathway (cyp2j↑ → 11,12-EET↑). Probiotics also enhanced Fe3+ sequestration (steap4↑) and antioxidant defense (CAT↑, gpx4a↑), limiting Fenton reaction-mediated oxidative injury, and restored hepatic TG synthesis through upregulation of the DHAP-to-TG cascade (DHAP—(gpd1b↑) → G3P↑—(gpat3↑) → LPA—(agpat6↑) → PA—(plpp7↑) → DAG↑—(dgat2↑) → TG↑). These findings suggest that NP induces hepatotoxicity in S. meridionalis, involving ferroptosis, AA metabolism disruption and impaired TG synthesis as interconnected pathological events. Probiotics likely counteract this toxicity through systemic metabolic reprogramming. Collectively, these findings elucidate the hepatotoxic mechanisms of NP in S. meridionalis and offer toxicological data for its risk assessment, supporting the potential of probiotic-based strategies to mitigate emerging pollutant impacts in aquatic organisms.