Systematic impacts of fluoride exposure on the metabolomics of rats

Zhao, Shiyuan; Guo, Jinxiu; Xue, Hongjia; Meng, Junjun; Xie, Dadi; Liu, Xi; Yu, Qingqing; Zhong, Haitao; Jiang, Pei

doi:10.1016/j.ecoenv.2022.113888

Cited by 10 publications

(5 citation statements)

References 82 publications

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“…Previous studies have reported that fluoride exposure can lead to a reduction in amino acids in the heart, liver, and kidney of rats. Specifically, in the heart tissue of rats, L-serine, L-glutamine, L-aspartic acid, and L-glutamic acid exhibited decreased levels [52]. Consistent with these findings, among the DAMs identified in the fluoride-exposed group, a total of 39 metabolites in both PIM and NIM were found to be involved in amino acids metabolism.…”

Section: Discussionsupporting

confidence: 70%

“…Metabolomics serves as a rapid and highly sensitive approach for the investigation of a multitude of differentially abundant metabolites (DAMs). While the toxic effects of fluoride on serum [19,50], tissues [52] and cells [51] are gradually emerging, there is a notable absence of information regarding the metabolites in VSMCs exposed to fluoride. This study seeks to uncover changes in metabolites within VSMCs treated with fluoride, with the hope of offering novel insights and potential avenues for future research, possibly leading to more effective therapies.…”

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confidence: 99%

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Fluoride impairs vascular smooth muscle A7R5 cell lines via disrupting amino acids metabolism

Li,

Yang,

et al. 2024

J Transl Med

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Given the insidious and high-fatality nature of cardiovascular diseases (CVDs), the emergence of fluoride as a newly identified risk factor demands serious consideration alongside traditional risk factors. While vascular smooth muscle cells (VSMCs) play a pivotal role in the progression of CVDs, the toxicological impact of fluoride on VSMCs remains largely uncharted. In this study, we constructed fluorosis model in SD rats and A7R5 aortic smooth muscle cell lines to confirm fluoride impaired VSMCs. Fluoride aggravated the pathological damage of rat aorta in vivo. Then A7R5 were exposed to fluoride with concentration ranging from 0 to 1200 μmol/L over a 24-h period, revealing a dose-dependent inhibition of cell proliferation and migration. The further metabolomic analysis showed alterations in metabolite profiles induced by fluoride exposure, notably decreasing organic acids and lipid molecules level. Additionally, gene network analysis underscored the frequency of fluoride's interference with amino acids metabolism, potentially impacting the tricarboxylic acid (TCA) cycle. Our results also highlighted the ATP-binding cassette (ABC) transporters pathway as a central element in VSMC impairment. Moreover, we observed a dose-dependent increase in osteopontin (OPN) and α-smooth muscle actin (α-SMA) mRNA level and a dose-dependent decrease in ABC subfamily C member 1 (ABCC1) and bestrophin 1 (BEST1) mRNA level. These findings advance our understanding of fluoride as a CVD risk factor and its influence on VSMCs and metabolic pathways, warranting further investigation into this emerging risk factor.

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Section: Discussionsupporting

confidence: 70%

mentioning

confidence: 99%

Fluoride impairs vascular smooth muscle A7R5 cell lines via disrupting amino acids metabolism

Li,

Yang,

et al. 2024

J Transl Med

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“…Several experimental studies in rodents have recently been conducted with the combined exposure of iAs and iF, evaluating the effect of iAs and iF, individually or together, on oxidative stress, inflammation, and reproductive and neurotoxicological effects, and they concluded that the simultaneous administration of iAs and iF is less toxic [ 22 – 25 ]. A limitation in these studies is that they used high concentrations of the same exposure magnitude for both pollutants when it is known that iF is usually in concentrations 50 to 150 times higher compared to iAs.…”

Section: Discussionmentioning

confidence: 99%

Decreased Arsenic Disposition and Alteration of its Metabolic Profile in mice Coexposed to Fluoride

Peña

Hernández

Razo

2023

Biol Trace Elem Res

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Inorganic arsenic (iAs) and fluoride (iF) are ubiquitous elements whose coexistence is frequent in several regions of the world due to the natural contamination of water sources destined for human consumption. It has been reported that coexposure to these two elements in water can cause toxic effects on health, which are controversial since antagonistic and synergistic effects have been reported. However, there is little information on the possible toxicological interaction between concurrent exposure to iAs and iF on the iAs metabolism profile.The goal of this study was to determine the effect of iF exposure on iAs methylation patterns in the urine and the tissues of female mice of the C57BL/6 strain, which were divided into four groups and exposed daily for 10 days through drinking water as follows: purified water (control); arsenite 1 mg/L, fluoride 50 mg/L and arsenite & fluoride 1:50 mg/L.To characterize the iAs methylation pattern in concomitant iF exposure, iAs and its methylated metabolites (MAs and DMAs) were quantified in the tissues and the urine of mice was exposed to iAs alone or in combination. Our results showed a statistically significant decrease in the arsenic species concentrations and altered relative proportions of arsenic species in tissues and urine in the As-iF coexposure group compared to the iAs-exposed group. These findings show that iF exposure decreases arsenic disposition and alters methylation capacity.Nevertheless, additional studies are required to elucidate the mechanisms involved in the iAs-iF interaction through iF exposure affecting iAs disposition and metabolism.

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“…According to epidemiological investigations and in vitro and in vivo experimental studies, fluorosis may cause a certain degree of damage to the liver, inducing hepatic glucose and lipid metabolic dysfunction, and at the cellular level, fluorosis can cause swelling of the endoplasmic reticulum and mitochondria, reduced nuclear volume, nuclear membrane wrinkling and other defects in hepatocytes [ 20 , 21 ]. Fluorosis was shown to increase the levels of inflammatory factors [ 22 ]. However, the pathogenesis of the resulting liver inflammation is unclear.…”

Section: Introductionmentioning

confidence: 99%

Expression of SDF-1/CXCR4 and related inflammatory factors in sodium fluoride-treated hepatocytes

Yang,

Shen,

Wang

et al. 2024

PLoS ONE

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At present, the mechanism of fluorosis-induced damage to the hepatic system is unclear. Studies have shown that excess fluoride causes some degree of damage to the liver, including inflammation. The SDF-1/CXCR4 signaling axis has been reported to have an impact on the regulation of inflammation in human cells. In this study, we investigated the role of the SDF-1/CXCR4 signaling axis and related inflammatory factors in fluorosis through in vitro experiments on human hepatic astrocytes (LX-2) cultured with sodium fluoride. CCK-8 assays showed that the median lethal dose at 24 h was 2 mmol/l NaF, and these conditions were used for subsequent enzyme-linked immunosorbent assays (ELISAs) and quantitative real-time polymerase chain reaction (qPCR) analysis. The protein expression levels of SDF-1/CXCR4 and the related inflammatory factors nuclear factor-κB (NF-κB), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin 1β (IL-1β) were detected by ELISAs from the experimental and control groups. The mRNA expression levels of these inflammatory indicators were also determined by qPCR in both groups. Moreover, the expression levels of these factors were significantly higher in the experimental group than in the control group at both the protein and mRNA levels (P < 0.05). Excess fluorine may stimulate the SDF-1/CXCR4 signaling axis, activating the inflammatory NF-κB signaling pathway and increasing the expression levels of the related inflammatory factors IL-6, TNF-α and IL-1β. Identification of this mechanism is important for elucidating the pathogenesis of fluorosis-induced liver injury.

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Systematic impacts of fluoride exposure on the metabolomics of rats

Cited by 10 publications

References 82 publications

Fluoride impairs vascular smooth muscle A7R5 cell lines via disrupting amino acids metabolism

Fluoride impairs vascular smooth muscle A7R5 cell lines via disrupting amino acids metabolism

Decreased Arsenic Disposition and Alteration of its Metabolic Profile in mice Coexposed to Fluoride

Expression of SDF-1/CXCR4 and related inflammatory factors in sodium fluoride-treated hepatocytes

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