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Chronic fluoride exposure induces tissue damage, oxidative stress, and immune dysfunction in juvenile crucian carp (Carassius auratus).
| Fish Physiology and Biochemistry | Zhang J, Gao X, Ma J, Wu L, Shi X, Su Q, Li X, Li Y. | 52:78.
Immune System Kidney Liver Oxidative Stress Animal Study

Abstract

Original abstract online at
https://link.springer.com/article/10.1007/s10695-026-01697-x

Fluoride pollution in aquatic ecosystems poses substantial risks to aquatic organisms. However, most previous studies have focused on acute toxicity and skeletal fluorosis, whereas the chronic toxic effects of fluoride on non-skeletal tissues in fish remain poorly understood. In particular, the mechanisms underlying fluoride-induced toxicity, especially those associated with immune dysfunction and intestinal microbiota disruption, have yet to be fully elucidated. In the present study, juvenile crucian carp (Carassius auratus) were used as an experimental model to investigate the chronic toxic effects of fluoride on aquatic organisms. Fish were divided into four groups: a control group, an environmentally relevant NaF group (5 mg/L), and two sub-lethal NaF exposure groups (50 and 95 mg/L). Samples were collected at 45 and 90 days post-exposure. The results showed that exposure to fluoride resulted in significant pathological damage to gill, liver, intestine, and kidney tissues in a dose- and time-dependent manner. After 90 days of fluoride exposure, the activities of antioxidant enzymes (CAT, SOD) and T-AOC in the gill, liver, intestine, and kidney were inhibited, while MDA levels were markedly increased, indicating enhanced oxidative stress. Meanwhile, the expression of immune-related genes, including NF-xB, IL-1, TNF-a, IL-8, C3, and LYZ-C, was significantly downregulated in the 5 and 50 mg/L groups but markedly upregulated in the 95 mg/L group, indicating a dose-dependent immune response. In addition, 16S rRNA sequencing showed that fluoride exposure induced gut microbiota dysbiosis, characterized by an increased abundance of potential pathogens Alsobacter and a reduced abundance of beneficial bacteria Gemmobacter and Dinghuibacter. Such dysbiosis may impair intestinal barrier function and disturb local immune homeostasis, thereby contributing to the altered immune responses. Overall, this study provides new insights into the molecular mechanisms underlying the chronic toxicity of fluoride in fish, particularly in non-skeletal tissues and the immune system, and highlights the ecological risks associated with long-term fluoride exposure in aquatic environments.

Funding

This project was fully sponsored by the Natural Science Foundation of Henan Province (242300420164), the Special Fund for Henan Agriculture Research System (HARS-22–16-G1), and the Key Program of Higher Education of Henan Province (222102110345).

Author information

Authors and Affiliations

  1. Engineering Lab of Henan Province for Aquatic Animal Disease Control, Engineering Technology Research Center of Henan Province for Aquatic Animal Cultivation, College of Fisheries, Henan Normal University, Xinxiang, 453007, People’s Republic of China

    Jingjing Zhang, Jun Ma, Limin Wu, Xi Shi, Qing Su, Xuejun Li & Yongjing Li

  2. Observation and Research Station On Water Ecosystem in Danjiangkou Reservoir of Henan Province, Nanyang, Henan, 474450, People’s Republic of China

    Limin Wu, Xi Shi, Xuejun Li & Yongjing Li

  3. College of Life Science, Henan Normal University, Xinxiang, 453007, People’s Republic of China

    Qing Su & Yongjing Li

  4. Yellow River Engineering Consulting Co., Ltd., Zhengzhou, 450003, People’s Republic of China

    Xuejun Gao

Contributions

Jingjing Zhang: Investigation, Methodology, Formal analysis, Writing—Original Draft. Xuejun Gao: Jun Ma: Investigation, Methodology, Data curation. Investigation, Formal analysis, Data curation. Limin Wu: Formal analysis, Data curation, Funding acquisition. Xi Shi: Data curation. Qing Su: Data curation. Xuejun Li: Visualization, supervision, conceptualization, and funding acquisition. Yongjing Li: Writing—review and editing, investigation, methodology, supervision, visualization, and validation. All the authors have read and agreed to the published version of the manuscript.

Corresponding authors

Correspondence to Xuejun Li or Yongjing Li.

Ethics declarations

Ethical approval

All experiments in this study strictly adhered to the ethical guidelines of the Ethics Committee of Henan Normal University (HNSD-2019–03-02). In the actual operation, the animal rearing environment, experimental procedures, and disposal methods were strictly implemented in accordance with the approved protocols to minimize the pain and discomfort of the animals to the greatest extent possible.

Competing interests

The authors declare no competing interests.

Supplementary Information

Below is the link to the electronic supplementary material.

ESM1 (download DOCX )

(DOCX 413 KB)

Data availability

No datasets were generated or analyzed during the current study.

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Cite this article

Zhang, J., Gao, X., Ma, J. et al. Chronic fluoride exposure induces tissue damage, oxidative stress, and immune dysfunction in juvenile crucian carp (Carassius auratus). Fish Physiol Biochem 52, 78 (2026). https://doi.org/10.1007/s10695-026-01697-x