Sodium fluoride induces apoptosis in the kidney of rats through caspase-mediated pathways and DNA damage

Song, Guo Hua; Gao, Junfang; Wang, Chun Fang; Chen, Chao Yang; Yan, Xiao; Guo, Min; Wang, Yu; Huang, Fu Bing

doi:10.1007/s13105-014-0354-z

Cited by 63 publications

(33 citation statements)

References 31 publications

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“…It has been reported that fluoride can induce DNA damage in the kidney [28,29]. DNA damage generally results in the activation of the ATM-dependent signaling pathway [40].…”

Section: Discussionmentioning

confidence: 99%

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

Luo

Guo

Kuang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Excessive fluoride intake can induce cytotoxicity, DNA damage and cell-cycle changes in many tissues and organs, including the kidney. However, the underlying molecular mechanisms of fluoride-induced renal cell-cycle changes are not well understood at present. In this study, we used a mouse model to investigate how sodium fluoride (NaF) induces cell-cycle changes in renal cells. Methods: Two hundred forty ICR mice were randomly assigned to four equal groups for intragastric administration of NaF (0, 12, 24 and 48 mg/kg body weight/day) for 42 days. Kidneys were taken to measure changes of the cell-cycle at 21 and 42 days of the experiment, using flow cytometry, quantitative real-time polymerase chain reaction (qRT-PCR) and western blot methods. Results: NaF, at more than 12 mg/kg body weight, induced G2/M phase cell-cycle arrest in the renal cells, which was supported by the finding of significantly increased percentages of renal cells in the G2/M phase. We found also that G2/M phase cell-cycle arrest was accompanied by up-regulation of p-ATM, p-Chk2, p-p53, p-Cdc25C, p-CDK1, p21, and Gadd45a protein expression levels; up-regulation of ATM, Chk2, p53, p21, and Gadd45a mRNA expression levels; down-regulation of CyclinB1, mdm2, PCNA protein expression levels; and down-regulation of CyclinB1, CDK1, Cdc25C, mdm2, and PCNA mRNA expression levels. Conclusion: In this mouse model, NaF, at more than 12 mg/ kg, induced G2/M phase cell-cycle arrest by activating the ATM-Chk2-p53/Cdc25C signaling pathway, which inhibits the proliferation of renal cells and development of the kidney. Activation of the ATM-Chk2-p53/Cdc25C signaling pathway is the mechanism of NaF-induced renal G2/M phase cell-cycle arrest in this model.

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“…It has been reported that fluoride can induce DNA damage in the kidney [28,29]. DNA damage generally results in the activation of the ATM-dependent signaling pathway [40].…”

Section: Discussionmentioning

confidence: 99%

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

Luo

Guo

Kuang

et al. 2018

Cell Physiol Biochem

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“…Likewise, several studies estimated damaged DNA and their levels with mice kidneys by the comet assay at different concentrations of NaF (4, 12, 20mg/L; 50, 100, 200 mg/L) [30,31]. Some of these studies revealed that varying degrees of DNA damage in kidney apoptosis were found in renal cells, which induced by 50, 100, 200 mg/L NaF [31]. And several studies proved that DNA damaged in SO 2 induced mice kidney for 7 days (125, 250, 500 mg/kg body weight) [24].…”

Section: Discussionmentioning

confidence: 99%

Combination of Fluoride and SO2 Induce DNA Damage and Morphological Alterations in Male Rat Kidney

Gao

Liang

Zhang

et al. 2018

Cell Physiol Biochem

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Background/Aims: We investigated the combined toxic effect of sodium fluoride (NaF) and sulfur dioxide (SO₂) on kidney morphological changes and DNA damage in male Wistar rats. Methods: In this study we selected totally 96 male Wistar rats (12-week-old) then randomly group-housed them into four cages, treated with deionized water, NaF, SO₂ and co-treatment of NaF and SO₂ respectively. Morphological changes of kidney were detected by hematoxylin and eosin (H&E) staining at 2, 4, 6 and 8 weeks. Correspondingly, tailing ratio and comet length were measured by BAB Bs Comet Assay System, including DNA damage special unit were calculated to evaluate the grades of kidney DNA damage at the same time. Results: Treated groups showed a body weight decrease when compared to control group. However, no significant difference in the relative weight of kidney was found in all four groups. It is noteworthy that at 2, 4, 6 and 8 weeks after exposure, the morphological alteration of renal tubules were observed in all treated groups, especially in group-IV. Also, at 4 and 6 weeks, notable DNA damage was found in all treated groups, as assessed by significantly increasing trend of comet length tailing ratio. Conclusion: The study manifests that presence of NaF and SO₂ will not only induce renal tissue lesions but also impact DNA integrity. In addition, this combined exposure exhibits a synergistic effect, characterizing a dose-dependence and time correlation. These findings may provide novel insights regarding perturbations of DNA damage and its functions as a potential new mechanism, by which cautious interpretation of NaF and SO₂ co-exposure evolved in both animals and human beings is necessary.

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“…Therefore, 8-OHdG in serum, urine or tissue was routinely used as a biomarker for DNA damage and carcinogenesis. Previous animal experiment data showed that NaF exhibited genotoxic activity in bone marrow, liver and kidney cells by the comet assay [34][35][36]. Nevertheless, some rodent studies suggested NaF did not result in systemic genotoxic effect in multiple organs, including liver and kidney [37], which had contradiction between these researches.…”

Section: Sub-chronic Fluorosis Caused Oxidative Stress and Dna Damagementioning

confidence: 97%

Ameliorative effects of N-acetylcysteine on fluoride-induced oxidative stress and DNA damage in male rats’ testis

Feng

Huang

Yang

et al. 2015

Mutation Research/Genetic Toxicology and Environmental Mutagene

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Sodium fluoride induces apoptosis in the kidney of rats through caspase-mediated pathways and DNA damage

Cited by 63 publications

References 31 publications

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

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

Combination of Fluoride and SO2 Induce DNA Damage and Morphological Alterations in Male Rat Kidney

Ameliorative effects of N-acetylcysteine on fluoride-induced oxidative stress and DNA damage in male rats’ testis

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