Sodium fluoride (NaF) causes toxic effects on splenic development in mice

Abstract

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.

Sodium Fluoride Arrests Renal G2/M Phase Cell-Cycle Progression by Activating ATM-Chk2-P53/Cdc25C Signaling Pathway in Mice

“…PCNA is an essential processivity factor for DNA polymerases, and it also is an index of cell proliferation [61]. Viscera index is usually used to assess the toxic effects of medicines and the development of living tissue [19,62]. In this study, the mRNA and protein expression levels of PCNA and the renal viscera index were reduced in the 24 and 48 mg/kg groups, suggesting that the proliferation of renal cells and development of the kidney were suppressed.…”

Chronic Exposure to Sodium Fluoride Triggers Oxidative Biochemistry Misbalance in Mice: Effects on Peripheral Blood Circulation

“…Several studies reported fluoride as an inducer of oxidative stress and modulator of intracellular redox homeostasis, lipid peroxidation, and protein carbonyl content [ 7 , 49 , 50 ]. These processes occur due to the ability to break hydrogen bonds in proteins (e.g., in the enzyme active center), as well as increasing the mitochondrial generation of free radicals resulting in oxidative stress, mitochondrial DNA degradation, and cell death [ 10 , 63 , 64 ].…”

“…For example, fluoride at lower concentrations ( μ M) acts as a stimulator and promotes cell proliferation, while at higher concentrations (mM), it inhibits enzyme action, including phosphatases [ 7 , 8 ]. In addition, high doses of ingested fluoride might damage several biological systems, including the central nervous system [ 9 ], reduction of splenic and humoral cell immunity [ 10 ], dysfunction of the male reproductive system [ 11 ], and liver damage [ 12 , 13 ]. Evidence in animal models suggests that fluoride concentrations above 5 mg/L in drinking water can modify cellular processes such as respiration and metabolism, thus leading to oxidative stress [ 7 ].…”

Moringa Oleifera Leaf Extract Repairs the Oxidative Misbalance following Sub-Chronic Exposure to Sodium Fluoride in Nile Tilapia Oreochromis niloticus

“…In different words, low concentration of fluoride (µM) might act as a promoter for cell proliferation and enzymatic activity; however, a high concentration of fluoride (mM) could act as an enzymatic inhibitor. This enzyme inhibitory action occurred due to the strong electronegativity of fluoride, where it forms ions and interacts with enzymes leading to toxicity and biological damage to different body systems [9], such as the central nervous system [10], spleen and immune organs [11], the male reproductive system [12], and the liver [13,14].…”