Rutin Inhibits Histamine-Induced Cytotoxicity of Zebrafish Liver Cells via Enhancing Antioxidant and Anti-Inflammatory Properties

Histamine can damage the antioxidant and immune systems in fish and crustaceans. Rutin, a natural substance with a diverse phenolic structure, has demonstrated antioxidant and anti-inflammatory properties. However, whether rutin can mitigate histamine-induced negative effects remains uninvestigated in fish models. This study investigated the effect of 0.1–100 μM rutin preincubation on histamine (29.5 mM)-induced cytotoxicity in zebrafish liver cells (ZFL) and its potential mechanisms. Results showed that 0.1–100 μM rutin significantly improved ZFL cell survival following histamine stimulation and protected cellular morphology. Rutin inhibited the adverse effects of histamine on ZFL by scavenging or suppressing the accumulation of reactive oxygen species (ROS), H2O2, and malondialdehyde (MDA), while increasing the activities of superoxide dismutase (SOD), catalase (CAT), and total antioxidant capacity (T-AOC). At the protein level, 10 μM rutin significantly promoted Nrf2 protein expression. HO-1 protein was significantly up-regulated after preincubation with 0.1–10 μM rutin, whereas IL-1β protein levels were significantly down-regulated. The mechanism may involve activation of the Nrf2 antioxidant signaling pathway and inhibition of the NF-κB inflammatory signaling pathway. In summary, within the experimental concentration range, 10 μM rutin showed the strongest inhibitory effects on histamine-induced ZFL cell death and oxidative stress. This study provides a theoretical basis and data support for evaluating rutin’s feasibility as a green aquatic feed additive.