Fluoride exposure altered metabolomic profile in rat serum

Yue, Baijuan; Zhang, Xuhua; Li, Wanpan; Wang, Jundong; Sun, Zilong; Niu, Ruiyan

doi:10.1016/j.chemosphere.2020.127387

Cited by 11 publications

(8 citation statements)

References 36 publications

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“…Those results revealed that the MT alleviated the As 3+ -induced metabolism distortion of the amino acid. 37 MT Alleviated As 3+ -Induced Energy Metabolism Disorder. The TCA cycle and glycolysis were perturbed after As 3+ exposure.…”

Section: ■ Results and Discussionmentioning

confidence: 98%

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Metallothionein Attenuated Arsenic-Induced Cytotoxicity: The Underlying Mechanism Reflected by Metabolomics and Lipidomics

Wang

et al. 2021

J. Agric. Food Chem.

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Arsenic ions (As3+) have been recognized as a hazard that threatens the health of humans. Metallothionein (MT) rich in cysteine may provide favorable binding sites for chelation of As3+. However, the influence of MT on As3+-induced toxicity and the underlying mechanism are poorly understood, especially at the metabolic level. Herein, the effects of MT on As3+-induced toxicity were evaluated. Cell viability analysis suggested that MT alleviated As3+-induced cytotoxicity. The metabolic response of PC12 cells to As3+ investigated by lipidomics and metabolomics indicated that the presence of As3+ disrupted phospholipids metabolism and induced cell membrane damage. Moreover, energy and amino acid metabolism were perturbed by As3+. The perturbation of As3+ on metabolism was further illustrated by the decrease of the mitochondrial membrane potential and the rise of cellular reactive oxygen species (ROS). On the contrary, MT rescued As3+-induced metabolic disorder and suppressed ROS accumulation. In addition, the binding process between As3+ and MT was characterized. The results proved that the As3+–MT complex was formed and chelated As3+-scavenged ROS, thus alleviating the toxic effects of As3+. These results revealed that MT would be a potential agent to reduce As3+-induced cytotoxicity.

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Section: ■ Results and Discussionmentioning

confidence: 98%

“…N -Acetyl- l -ornithine also increased significantly under As 3+ stress compared with the control group, while it decreased significantly in the MT–As 3+ -treated group compared with that in As 3+ -treated group (Figure S6A). Those results revealed that the MT alleviated the As 3+ -induced metabolism distortion of the amino acid …”

Section: Resultsmentioning

confidence: 98%

Metallothionein Attenuated Arsenic-Induced Cytotoxicity: The Underlying Mechanism Reflected by Metabolomics and Lipidomics

Wang

et al. 2021

J. Agric. Food Chem.

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“…Macrophage polarization plays a fundamental role in the quality and effectiveness of injury repair [ 5 ]. Fluoride exhibits diverse effects on immune cell metabolism and function [ 14 , 19 , 20 ] and has been proposed as a potential regulator of bone tissue regeneration. Thus, the modification of biomaterials with fluoride may be a promising strategy for modulating the osteoimmunology environment by regulating immunometabolism.…”

Section: Discussionmentioning

confidence: 99%

“…Fluoride plays a crucial role in the regulation of bone tissue regeneration, repair, and remodeling [ 14 , 17 ]. Notably, fluoride exerts its effects in a concentration-dependent manner within the human body [ 18 ], which shows diverse effects on the metabolism and function of immune cells [ 14 , 19 , 20 ]. Appropriate concentration of fluoride ions was demonstrated to enhanced M2 macrophage polarization [ 21 ], via a potential metabolic pathway including the mitochondrial tricarboxylic acid (TCA) cycle and OxPhos [ 14 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

Fluorinated hydroxyapatite conditions a favorable osteo-immune microenvironment via triggering metabolic shift from glycolysis to oxidative phosphorylation

Chen,

Ha,

et al. 2024

J Transl Med

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Background Biological-derived hydroxyapatite is widely used as a bone substitute for addressing bone defects, but its limited osteoconductive properties necessitate further improvement. The osteo-immunomodulatory properties hold crucial promise in maintaining bone homeostasis, and precise modulation of macrophage polarization is essential in this process. Metabolism serves as a guiding force for immunity, and fluoride modification represents a promising strategy for modulating the osteoimmunological environment by regulating immunometabolism. In this context, we synthesized fluorinated porcine hydroxyapatite (FPHA), and has demonstrated its enhanced biological properties and osteogenic capacity. However, it remains unknown whether and how FPHA affects the immune microenvironment of the bone defects. Methods FPHA was synthesized and its composition and structural properties were confirmed. Macrophages were cultured with FPHA extract to investigate the effects of FPHA on their polarization and the related osteo-immune microenvironment. Furthermore, total RNA of these macrophages was extracted, and RNA-seq analysis was performed to explore the underlying mechanisms associated with the observed changes in macrophages. The metabolic states were evaluated with a Seahorse analyzer. Additionally, immunohistochemical staining was performed to evaluate the macrophages response after implantation of the novel bone substitutes in critical size calvarial defects in SD rats. Results The incorporation of fluoride ions in FPHA was validated. FPHA promoted macrophage proliferation and enhanced the expression of M2 markers while suppressing the expression of M1 markers. Additionally, FPHA inhibited the expression of inflammatory factors and upregulated the expression of osteogenic factors, thereby enhancing the osteogenic differentiation capacity of the rBMSCs. RNA-seq analysis suggested that the polarization-regulating function of FPHA may be related to changes in cellular metabolism. Further experiments confirmed that FPHA enhanced mitochondrial function and promoted the metabolic shift of macrophages from glycolysis to oxidative phosphorylation. Moreover, in vivo experiments validated the above results in the calvarial defect model in SD rats. Conclusion In summary, our study reveals that FPHA induces a metabolic shift in macrophages from glycolysis to oxidative phosphorylation. This shift leads to an increased tendency toward M2 polarization in macrophages, consequently creating a favorable osteo-immune microenvironment. These findings provide valuable insights into the impact of incorporating an appropriate concentration of fluoride on immunometabolism and macrophage mitochondrial function, which have important implications for the development of fluoride-modified immunometabolism-based bone regenerative biomaterials and the clinical application of FPHA or other fluoride-containing materials. Graphical Abstract. FPHA was successfully prepared through the chemical and thermal process. The immunomodulatory effects of FPHA were investigated through in vitro and in vivo studies, revealing its ability to induce a metabolic shift in macrophages from glycolysis to mitochondrial oxidative phosphorylation (OxPhos). This metabolic remodeling resulted in a notable suppression of M1 macrophage polarization and promotion of M2 macrophage polarization. Furthermore, FPHA was found to enhance osteogenic differentiation and facilitate bone repair. These findings underscore the promising potential of FPHA as a biomaterial for bone regenerative applications, providing valuable insights for the development of bioactive materials with metabolic-immunoregulatory properties Graphical Abstract

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“…This study showed that the excessive intake of fluoride affects the expression of proteins and metabolites in the blood. Fluoride can alter the expression levels of nicotinamide, adenosine, 1-oleoyl-sn-glycero-3-phosphocholine, and 1-stearoyl-sn-glycerol 3-phosphocholine metabolites in the serum, leading to bone-related diseases [ 19 ]. The activation of the HIF-1 signal pathway and enhancement of glycolysis/gluconeogenesis are the signs of the activation of immune and inflammatory cells, and the metabolic pathways are changed in response to hypoxia [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

Role of Glycolysis/Gluconeogenesis and HIF-1 Signaling Pathways in Rats with Dental Fluorosis Integrated Proteomics and Metabolomics Analysis

Yang

et al. 2022

IJMS

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Fluoride is widely distributed, and excessive intake will lead to dental fluorosis. In this study, six offspring rats administrated 100 mg/L sodium fluoride were defined as the dental fluorosis group, and eight offspring rats who received pure water were defined as the control group. Differentially expressed proteins and metabolites extracted from peripheral blood were identified using the liquid chromatography tandem mass spectrometry and gas chromatography mass spectrometry, with the judgment criteria of fold change >1.2 or <0.83 and p < 0.05. A coexpression enrichment analysis using OmicsBean was conducted on the identified proteins and metabolites, and a false discovery rate (FDR) < 0.05 was considered significant. Human Protein Atlas was used to determine the subcellular distribution of hub proteins. The Gene Cards was used to verify results. A total of 123 up-regulated and 46 down-regulated proteins, and 12 up-regulated and 2 down-regulated metabolites were identified. The significant coexpression pathways were the HIF-1 (FDR = 1.86 × 10−3) and glycolysis/gluconeogenesis (FDR = 1.14 × 10−10). The results of validation analysis showed the proteins related to fluorine were mainly enriched in the cytoplasm and extrinsic component of the cytoplasmic side of the plasma membrane. The HIF-1 pathway (FDR = 1.01 × 10−7) was also identified. Therefore, the HIF-1 and glycolysis/gluconeogenesis pathways were significantly correlated with dental fluorosis.

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Fluoride exposure altered metabolomic profile in rat serum

Cited by 11 publications

References 36 publications

Metallothionein Attenuated Arsenic-Induced Cytotoxicity: The Underlying Mechanism Reflected by Metabolomics and Lipidomics

Metallothionein Attenuated Arsenic-Induced Cytotoxicity: The Underlying Mechanism Reflected by Metabolomics and Lipidomics

Fluorinated hydroxyapatite conditions a favorable osteo-immune microenvironment via triggering metabolic shift from glycolysis to oxidative phosphorylation

Role of Glycolysis/Gluconeogenesis and HIF-1 Signaling Pathways in Rats with Dental Fluorosis Integrated Proteomics and Metabolomics Analysis

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