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Volume 10
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10.3390/fishes10080408
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Article

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

by
Ke Cheng
1,2,
Apeng Liu
3,
Di Peng
2,
Lixue Dong
2,
Yangyang Liu
2,
Juan Tian
2,
Hua Wen
2,
Yongju Luo
1,
Zhongbao Guo
1,* and
Ming Jiang
2,*
1
China (Guangxi)-ASEAN Key Laboratory of Comprehensive Exploitation and Utilization of Aquatic Germplasm Resources, Ministry of Agriculture and Rural Affairs, Key Laboratory of Aquaculture Genetic and Breeding and Healthy Aquaculture of Guangxi Academy of Fishery Sciences, Nanning 530021, China
2
Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan 430223, China
3
Shenzhen Aohua Group Co., Ltd., Shenzhen 518054, China
*
Authors to whom correspondence should be addressed.
Fishes 2025, 10(8), 408; https://doi.org/10.3390/fishes10080408
Submission received: 4 July 2025 / Revised: 5 August 2025 / Accepted: 12 August 2025 / Published: 14 August 2025
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Abstract

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.
Keywords: rutin; histamine; Nrf2; NF-κB; zebrafish liver cells rutin; histamine; Nrf2; NF-κB; zebrafish liver cells
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MDPI and ACS Style

Cheng, K.; Liu, A.; Peng, D.; Dong, L.; Liu, Y.; Tian, J.; Wen, H.; Luo, Y.; Guo, Z.; Jiang, M. Rutin Inhibits Histamine-Induced Cytotoxicity of Zebrafish Liver Cells via Enhancing Antioxidant and Anti-Inflammatory Properties. Fishes 2025, 10, 408. https://doi.org/10.3390/fishes10080408

AMA Style

Cheng K, Liu A, Peng D, Dong L, Liu Y, Tian J, Wen H, Luo Y, Guo Z, Jiang M. Rutin Inhibits Histamine-Induced Cytotoxicity of Zebrafish Liver Cells via Enhancing Antioxidant and Anti-Inflammatory Properties. Fishes. 2025; 10(8):408. https://doi.org/10.3390/fishes10080408

Chicago/Turabian Style

Cheng, Ke, Apeng Liu, Di Peng, Lixue Dong, Yangyang Liu, Juan Tian, Hua Wen, Yongju Luo, Zhongbao Guo, and Ming Jiang. 2025. "Rutin Inhibits Histamine-Induced Cytotoxicity of Zebrafish Liver Cells via Enhancing Antioxidant and Anti-Inflammatory Properties" Fishes 10, no. 8: 408. https://doi.org/10.3390/fishes10080408

APA Style

Cheng, K., Liu, A., Peng, D., Dong, L., Liu, Y., Tian, J., Wen, H., Luo, Y., Guo, Z., & Jiang, M. (2025). Rutin Inhibits Histamine-Induced Cytotoxicity of Zebrafish Liver Cells via Enhancing Antioxidant and Anti-Inflammatory Properties. Fishes, 10(8), 408. https://doi.org/10.3390/fishes10080408

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