PMID- 34496328 OWN - NLM STAT- MEDLINE DCOM- 20210928 LR - 20210928 IS - 1879-1514 (Electronic) IS - 0166-445X (Linking) VI - 239 DP - 2021 Oct TI - Effects of cyclophosphamide on antioxidative and immune functions of Nile tilapia (Oreochromis Niloticus) via the TLR-NF-kappaB signaling pathway. PG - 105956 LID - S0166-445X(21)00215-0 [pii] LID - 10.1016/j.aquatox.2021.105956 [doi] AB - 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-kappaB 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, nfkappab1, nfkappab2, 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-kappaB signaling pathway. CI - Copyright (c) 2021. Published by Elsevier B.V. FAU - Cao, Li-Ping AU - Cao LP AD - Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture and Rural Affairs, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, wuxi 214081, China; International Joint Research Laboratory for Fish immunopharmacology, Chinese Academy of Fishery Sciences, wuxi 2140814, China. FAU - Du, Jin-Liang AU - Du JL AD - Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture and Rural Affairs, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, wuxi 214081, China; International Joint Research Laboratory for Fish immunopharmacology, Chinese Academy of Fishery Sciences, wuxi 2140814, China. FAU - Jia, Rui AU - Jia R AD - Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture and Rural Affairs, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, wuxi 214081, China; International Joint Research Laboratory for Fish immunopharmacology, Chinese Academy of Fishery Sciences, wuxi 2140814, China. FAU - Ding, Wei-Dong AU - Ding WD AD - Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture and Rural Affairs, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, wuxi 214081, China; International Joint Research Laboratory for Fish immunopharmacology, Chinese Academy of Fishery Sciences, wuxi 2140814, China. FAU - Xu, Pao AU - Xu P AD - Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture and Rural Affairs, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, wuxi 214081, China; International Joint Research Laboratory for Fish immunopharmacology, Chinese Academy of Fishery Sciences, wuxi 2140814, China. FAU - Yin, Guo-Jun AU - Yin GJ AD - Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture and Rural Affairs, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, wuxi 214081, China; International Joint Research Laboratory for Fish immunopharmacology, Chinese Academy of Fishery Sciences, wuxi 2140814, China. Electronic address: yingj@ffrc.cn. FAU - Zhang, Ting AU - Zhang T AD - The Affiliated Wuxi Matemity and Child Health Care Hospital of Nanjing Medical University, Wuxi 214002, China. Electronic address: zhangting040715@163.com. LA - eng PT - Journal Article DEP - 20210828 PL - Netherlands TA - Aquat Toxicol JT - Aquatic toxicology (Amsterdam, Netherlands) JID - 8500246 RN - 0 (Antioxidants) RN - 0 (NF-kappa B) RN - 0 (Water Pollutants, Chemical) RN - 8N3DW7272P (Cyclophosphamide) SB - IM MH - Animals MH - Antioxidants MH - *Cichlids/metabolism MH - Cyclophosphamide/toxicity MH - *Fish Diseases MH - Immunity MH - NF-kappa B/genetics/metabolism MH - Signal Transduction MH - *Water Pollutants, Chemical/toxicity OTO - NOTNLM OT - Cyclophosphamide OT - Immunosuppression OT - Oreochromis niloticus OT - TLR-NF-kappaB signaling pathway EDAT- 2021/09/09 06:00 MHDA- 2021/09/29 06:00 CRDT- 2021/09/08 20:08 PHST- 2021/05/19 00:00 [received] PHST- 2021/08/20 00:00 [revised] PHST- 2021/08/24 00:00 [accepted] PHST- 2021/09/09 06:00 [pubmed] PHST- 2021/09/29 06:00 [medline] PHST- 2021/09/08 20:08 [entrez] AID - S0166-445X(21)00215-0 [pii] AID - 10.1016/j.aquatox.2021.105956 [doi] PST - ppublish SO - Aquat Toxicol. 2021 Oct;239:105956. doi: 10.1016/j.aquatox.2021.105956. Epub 2021 Aug 28.