Sodium fluoride (NaF) causes toxic effects on splenic development in mice
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Ping Kuang1,*, Huidan Deng1,*, Hengmin Cui1,2, Lian Chen1, Jing Fang1,2, Zhicai Zuo1,2, Junliang Deng1,2, Xun Wang1,2, Ling Zhao1,2
1College of Veterinary Medicine, Sichuan Agricultural University, Ya’an 625014, China
2Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Sichuan Agricultural University, Ya’an 625014, China
*These authors contributed equally to this work
Hengmin Cui, email: [email protected]
Keywords: NaF, growth index, T and B-cell, cytokine, cell cycle
Received: November 07, 2016 Accepted: December 07, 2016 Published: December 16, 2016
At present, very limited studies focus on the toxic effect of sodium fluoride (NaF) on splenic development of human and animals in vivo. This study was firstly designed to evaluate the toxic effects of NaF on the splenic development of mice in vivo by observing histopathological lesions, changes of splenic growth index (GI), T and B cells, immunoglobulin A (IgA), immunoglobulin G (IgG) and immunoglobulin M (IgM) contents, cytokine protein expression levels, and cell cycle and cyclins/cdks protein expression levels using the methods of pathology, flow cytometry (FCM), western blot (WB), and enzyme-linked immunosorbent assay (ELISA). A total of 240 ICR mice were equally allocated into four groups with intragastric administration of distilled water in the control group and 12, 24, 48 mg/kg NaF solution in the experimental groups for 42 days. The results showed that NaF in 12 mg/kg and over caused the toxic effects on splenic development, which was characterized by reducing growth index and lymphocytes in the white and red pulp histopathologically, increasing cell percentages of the G0/G1 phase and decreasing cell percentages of the S phase, and reducing T cells and B cells as well as IgA, IgG, and IgM contents when compared with those in the control group. Concurrently, cytokines including interleukin-2 (IL-2), transforming growth factor beta (TGF-β), tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ) and cyclin (E/D and CDK2/4) protein expression levels were markedly decreased (P < 0.05 or P < 0.01), and interleukin-10 (IL-10) protein expression levels were significantly increased (P < 0.05 and P < 0.01) in the three NaF-treated groups. Toxic effects finally impaired the splenic cellular immunity and humoral immunity due to the reduction of T and B cell population and activity. Cell cycle arrest is the molecular basis of NaF-caused toxic effects on the splenic development.
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