4.7 Article

Effects of cyclophosphamide on antioxidative and immune functions of Nile tilapia (Oreochromis Niloticus) via the TLR-NF-ΚB signaling pathway

期刊

AQUATIC TOXICOLOGY
卷 239, 期 -, 页码 -

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ELSEVIER
DOI: 10.1016/j.aquatox.2021.105956

关键词

Cyclophosphamide; Oreochromis niloticus; Immunosuppression; TLR-NF-kappa B signaling pathway

资金

  1. Central Public-interest Scientific Institution Basal Research Fund, Freshwater Fisheries Research Center, CAFS [2019JBFM11]
  2. Jiangsu Science and Technology Department [BK20201143]
  3. Young Science-technology Talents Support Project of Jiansu Association Science and Technology [TJ-2021-076]

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The study found that cyclophosphamide treatment in fish induces cytotoxic effects on immune cells, lipid peroxidation, reduced antioxidant capacity, and inhibited immune function.
Intensive aquaculture often results in immunosuppression in fish, which may cause a series of diseases. In this study, to investigate the immunosuppressive mechanisms in fish, tilapia were intrapleural injected cyclophosphamide (CTX) at the doses of 10, 25, 50, 75 and 100 mg.kg(-1) to induce immunosuppression. We determined the viability of immune cells, the content of lysozyme (LZM) and immunoglobulin M (IgM), the levels of nitric oxide (NO) and antioxidant parameters. Meanwhile, the mRNA levels of complement C3 (c3), igm and the genes associated with the TLR-NF-kappa B signaling pathway in the head kidney (HK) and spleen were also determined. The results showed that CTX had a significant cytotoxic effect on peripheral blood leukocytes, HK macrophages and spleen cells in a dose-dependent manner. The protein and mRNA levels of C3 and IgM were down-regulated with the increase of CTX concentrations in serum, HK and/or spleen. The NO and LZM contents decreased significantly in HK and spleen after CTX treatments with 75 and 100 mg.kg(-1). CTX treatments with 50, 75 and/or 100 mg.kg(-1) markedly decreased the antioxidant ability and enhanced lipid peroxidation in HK and spleen. Furthermore, qPCR data showed that CTX treatments with 50-100 mg.kg(-1) clearly down-regulated the mRNA levels of tlr2, myd88, irak1, traf6, nf kappa b1, nf kappa b2, il-6, il-10 and tnf-alpha in the HK and/or spleen. Overall results suggested that CTX treatment had a cytotoxic effect on immune cells, induced lipid peroxidation, decreased the antioxidant capacity and inhibited immune function. The immunosuppressive mechanisms of CTX may be associated with the TLR-NF-kappa B signaling pathway.

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