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Fasakin OW, Awosika A, Ogunsanya ST, Benson IO, Olopoda AI. Anti-hypertensive effect of enriched white melon seed protein concentrate biscuit on sodium fluoride exposed rats. World J Exp Med 2025; 15:105798. [DOI: 10.5493/wjem.v15.i2.105798] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2025] [Revised: 03/12/2025] [Accepted: 03/24/2025] [Indexed: 04/16/2025] Open
Abstract
BACKGROUND Sodium fluoride (NaF) is a daily necessity consumed as the major ingredient of fluorinated drinking water, milk, salts, mouthwashes, toothpaste, and dentistry medications. However, the use of NaF products has also been associated with increased fluoride anion distribution in the body, leading to hypertension.
AIM This study evaluated the antihypertensive effect of sweet orange peels-enriched white melon seed protein concentrate (WSP) biscuit meal in eight-week-old albino rats exposed to NaF for 14 days.
METHODS Forty-two (42) male Wistar albino rats were assigned at random into 7 groups of 6 rats per group (control group and six experimental groups). The experimental groups received various treatments that lasted for two weeks. Twenty-four hours after the last administration, hemodynamic parameters were evaluated, rats were sacrificed, blood samples were collected, and the heart was harvested. Blood serum was assessed for cardiac troponin I (cTnI), creatine kinase-MB (CK-MB), and lactate dehydrogenase (LDH). At the same time, the heart homogenate was assayed for angiotensin-1 converting enzyme (ACE) activity, proinflammatory cytokines, nitric oxide concentrations, and antioxidant status. Cardiac tissues were stained with Hematoxylin and Eosin, Masson’s Trichrome, and cTnI. Also, the safety of the WSP biscuit diet was evaluated.
RESULTS Results obtained showed that NaF administration elevated the collagen content of cardiac tissues, activities of ACE, and concentrations of cTnI, CK-MB, LDH, tumor necrosis factor-alpha, and interleukin 1 beta, while there was a reduction in the concentration of nitric oxide and antioxidants; however, their alterations were significantly prevented in WSP-biscuit-fed rats. The WSP biscuit meal is safe for consumption and possesses dose-dependent antihypertensive ability at 10% and 20% inclusion.
CONCLUSION The WSP biscuit diet may be recommended in diet formulation for the management of individuals or communities that are predisposed to NaF contaminations.
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Affiliation(s)
- Olamide Wilson Fasakin
- Department of Biomedical Technology, Federal University of Technology, Akure 234034, Nigeria
| | - Ayoola Awosika
- College of Medicine, University of Illinois, Chicago, Peoria, IL 61601, United States
| | | | | | - Akinyode Isaac Olopoda
- Department of Biochemistry, Federal University of Technology, Akure 234034, Ondo, Nigeria
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Zhang C, Wang Y, Huang F, Zhang Y, Huang M, Liu H, Liu Y, Wang Q, Liu C, Angwa L, Gao Y, Sun D, Jiang Y. Novel mechanism of fluoride induced cardiovascular system injury by regulating p53/miR200c-3p during endothelial dysfunction. ENVIRONMENTAL RESEARCH 2025; 271:121102. [PMID: 39952459 DOI: 10.1016/j.envres.2025.121102] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/03/2024] [Revised: 02/02/2025] [Accepted: 02/10/2025] [Indexed: 02/17/2025]
Abstract
BACKGROUND The impairment of the cardiovascular system by fluoride has attracted public health concern, and its toxic effects on ECs have garnered extensive research attention. However, epidemiological clues of fluoride induced cardiovascular injury are limited. The function of ECs is crucial for the early diagnosis of CVD, yet mechanisms through which fluoride disrupts endothelial function are still unclear. PURPOSE To investigate the relationship between fluoride exposure and hypertension in population by epidemiological investigation. To explore the potential mechanism of functional injury of ECs induced by fluoride. RESULT Epidemiological studies have shown that the risk of hypertension in study population increased with the increased of urinary fluoride concentration [OR = 1.565, 95%CI (1.143, 2.142)]. In rat model with fluorosis alongside a model of fluoride induced ECs injury, NaF led to anti-adhesion of ECs and barrier dysfunction. Notably, the expression levels of eNOS and NO were found to be decreased, while the expression levels of ACE, vWF, ICAM-1, VCAM-1 and ET-1 were elevated. Our findings also indicated that NaF induced oxidative stress in ECs, evidenced by significant increased in ROS and MDA levels and decreased protein expression of GPx4 and SOD activity. It was further found that NaF activated the p53/miR-200c-3p signaling axis via ROS, leading to endothelial dysfunction. CONCLUSION This study found that fluoride exposure was a risk factor for hypertension. In addition, fluoride could cause ECs dysfunction by inducing oxidative stress and activating p53/miR-200c-3p. These findings were helpful to further understand the mechanism of fluoride induced cardiovascular system injury and provide a theoretical basis for fluoride induced cardiovascular system injury.
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Affiliation(s)
- Chao Zhang
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, People's Republic of China; NHC Key Laboratory of Etiology and Epidemiology(Harbin Medical University), People's Republic of China; Joint Key Laboratory of Endemic Diseases, Harbin Medical University, Guizhou Medical University, Xi'an Jiaotong University, People's Republic of China
| | - Yue Wang
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, People's Republic of China; NHC Key Laboratory of Etiology and Epidemiology(Harbin Medical University), People's Republic of China; Joint Key Laboratory of Endemic Diseases, Harbin Medical University, Guizhou Medical University, Xi'an Jiaotong University, People's Republic of China; Center for Chronic Disease Prevention and Control, Harbin Medical University, Harbin, People's Republic of China
| | - Fengya Huang
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, People's Republic of China; NHC Key Laboratory of Etiology and Epidemiology(Harbin Medical University), People's Republic of China; Joint Key Laboratory of Endemic Diseases, Harbin Medical University, Guizhou Medical University, Xi'an Jiaotong University, People's Republic of China; Center for Chronic Disease Prevention and Control, Harbin Medical University, Harbin, People's Republic of China
| | - Yaoyuan Zhang
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, People's Republic of China; NHC Key Laboratory of Etiology and Epidemiology(Harbin Medical University), People's Republic of China; Joint Key Laboratory of Endemic Diseases, Harbin Medical University, Guizhou Medical University, Xi'an Jiaotong University, People's Republic of China; Center for Chronic Disease Prevention and Control, Harbin Medical University, Harbin, People's Republic of China
| | - Mingyue Huang
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, People's Republic of China; NHC Key Laboratory of Etiology and Epidemiology(Harbin Medical University), People's Republic of China; Joint Key Laboratory of Endemic Diseases, Harbin Medical University, Guizhou Medical University, Xi'an Jiaotong University, People's Republic of China; Center for Chronic Disease Prevention and Control, Harbin Medical University, Harbin, People's Republic of China
| | - Hui Liu
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, People's Republic of China; Joint Key Laboratory of Endemic Diseases, Harbin Medical University, Guizhou Medical University, Xi'an Jiaotong University, People's Republic of China
| | - Yunzhu Liu
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, People's Republic of China; NHC Key Laboratory of Etiology and Epidemiology(Harbin Medical University), People's Republic of China; Joint Key Laboratory of Endemic Diseases, Harbin Medical University, Guizhou Medical University, Xi'an Jiaotong University, People's Republic of China
| | - Qiaoyu Wang
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, People's Republic of China; NHC Key Laboratory of Etiology and Epidemiology(Harbin Medical University), People's Republic of China; Joint Key Laboratory of Endemic Diseases, Harbin Medical University, Guizhou Medical University, Xi'an Jiaotong University, People's Republic of China
| | - Chang Liu
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, People's Republic of China; NHC Key Laboratory of Etiology and Epidemiology(Harbin Medical University), People's Republic of China; Joint Key Laboratory of Endemic Diseases, Harbin Medical University, Guizhou Medical University, Xi'an Jiaotong University, People's Republic of China
| | - Linet Angwa
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, People's Republic of China; United State University-Africa, Department of Phamaceutics, Pharmacy Practice, and Public Health, People's Republic of China
| | - Yanhui Gao
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, People's Republic of China; NHC Key Laboratory of Etiology and Epidemiology(Harbin Medical University), People's Republic of China; Joint Key Laboratory of Endemic Diseases, Harbin Medical University, Guizhou Medical University, Xi'an Jiaotong University, People's Republic of China; Center for Chronic Disease Prevention and Control, Harbin Medical University, Harbin, People's Republic of China.
| | - Dianjun Sun
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, People's Republic of China; NHC Key Laboratory of Etiology and Epidemiology(Harbin Medical University), People's Republic of China; Joint Key Laboratory of Endemic Diseases, Harbin Medical University, Guizhou Medical University, Xi'an Jiaotong University, People's Republic of China; Center for Chronic Disease Prevention and Control, Harbin Medical University, Harbin, People's Republic of China.
| | - Yuting Jiang
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, People's Republic of China; NHC Key Laboratory of Etiology and Epidemiology(Harbin Medical University), People's Republic of China; Joint Key Laboratory of Endemic Diseases, Harbin Medical University, Guizhou Medical University, Xi'an Jiaotong University, People's Republic of China; Center for Chronic Disease Prevention and Control, Harbin Medical University, Harbin, People's Republic of China.
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Mianeh HY, Amiri L, Jafari A, Nourozi N. Health risk assessment via Monte Carlo simulation and sensitivity analysis for fluoride and nitrate content in bottled waters consumed in Kermanshah city, Iran. Sci Rep 2025; 15:5008. [PMID: 39929929 PMCID: PMC11811224 DOI: 10.1038/s41598-025-89439-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2024] [Accepted: 02/05/2025] [Indexed: 02/13/2025] Open
Abstract
Bottled water consumption has increased in recent decade due to many reasons, especially significant decline in water quality and quantity. The concentration of fluoride and nitrate in bottled waters may vary based on brands and locations. This study was carried out to determine the levels of fluoride and nitrate in bottled waters consumed in Kermanshah city and assess the related non -carcinogenic risks. Totally, 22 brands of bottled water were collected from markets. Fluoride and nitrate measurement was conducted via a UV-visible spectrophotometer (DR-5000). From the results, Fluoride and nitrate levels in the studied bottled waters were 0.32 ± 0.18 mg/L and 2.3 ± 1.41 mg/L, respectively. The risk of non-carcinogenic in term of HQ for fluoride exposure, for only 2 brands of bottled water were > 1 for infants group. HQ was less than 1 for nitrate in all the brands for all the age groups revealed non-carcinogen risks. Hazard index (HI) calculation showed that only in 2 brands of bottled water HI was > 1 for infants group. The HI were as infants (0.64) > children (0.36) > teenagers (0.27) > adults (0.24). From Monte Carlo simulation, 95th Percentile for nitrate and fluoride was less than 1 for all the groups. This result indicated non-carcinogenic risks of nitrate and fluoride for 95% of the studied groups. Moreover, sensitivity analysis showered that concentration for both nitrate and fluoride had the highest effect on HQ for all the groups. From this work, although fluoride and nitrate content in the bottled waters were at standard range, but infants were proportionally at higher risk.
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Affiliation(s)
- Hanieh Yari Mianeh
- Department of Environmental Health Engineering, School of Health, Kermanshah University of Medical Sciences, Kermanshah, Iran
- Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Laya Amiri
- Department of Environmental Health Engineering, School of Health, Kermanshah University of Medical Sciences, Kermanshah, Iran
- Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Ali Jafari
- Department of Environmental Health Engineering, School of Health, Kermanshah University of Medical Sciences, Kermanshah, Iran.
- Health, Safety and Environment Technologies Research Core, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.
| | - Nasim Nourozi
- Department of Environmental Health Engineering, School of Health, Kermanshah University of Medical Sciences, Kermanshah, Iran
- Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran
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Wang G, Duan L, Du Y, Fu X, Liu B, Zhang X, Yu F, Zhou G, Ba Y. Serum calcium improves the relationship between fluoride exposure and hypothalamic-pituitary-testicular axis hormones levels in males-a cross-sectional study on farmers in the lower reaches of the Yellow River. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2024; 363:125084. [PMID: 39374768 DOI: 10.1016/j.envpol.2024.125084] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Revised: 09/13/2024] [Accepted: 10/04/2024] [Indexed: 10/09/2024]
Abstract
Numerous studies have reported the toxicity of fluoride to the male reproductive system, but epidemiological evidence is limited. We conducted a cross-sectional study in Kaifeng City, Henan Province in 2011 to explore the association between fluoride exposure and hypothalamic-pituitary-testicular (HPT) axis hormones in men. Morning urinary fluoride (UF), serum HPT axis hormones and serum calcium (SC) concentrations were detected. Percent changes and 95% confidence intervals in HPT axis hormones associated with UF were estimated using adjusted linear regression models, and performed subgroup analysis based on SC levels. The restricted cubic spline model was used to fit nonlinear relationships. For every 10% increase in UF, the concentrations of serum GnRH, T, SHBG and TSI decreased by 2.13%, 2.39%, 2.19% and 1.96%, while E2 and FEI increased by 1.11% and 3.33%. Subgroup analysis showed that for every 10% increase in UF, the levels of GnRH, T, TSI and FTI decreased by approximately 3.15%, 5.49%, 4.47% and 5.14%, while the E2 level increased by 2.92% in low-serum-calcium group (LCG). The levels of GnRH and T decreased by approximately 2.97% and 1.82% in medium-serum-calcium group (MCG). In high-serum-calcium group (HCG), serum SHBG levels decreased by 4.70%, while FTI and FEI levels increased by 4.93% and 4.20% as UF concentration increased (P < 0.05, respectively). The non-linear relationship between serum GnRH and UF concentrations presented an approximately inverted U-shaped curve, with a turning point UF concentration of 1.164 mg/L (P < 0.001), and their nonlinear relationship in LCG and MCG were similar to that in the overall subjects. In conclusion, excessive exposure to fluoride can interfere with male serum HPT axis hormones, and a moderate increase in SC alleviates the effect of fluoride. Prospective cohort studies are essential to confirm the causality.
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Affiliation(s)
- Guoqing Wang
- Department of Environmental Health, Zhengzhou University, Zhengzhou, Henan, 450001, China
| | - Leizhen Duan
- Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, Henan, 450001, China
| | - Yuhui Du
- Department of Environmental Health, Zhengzhou University, Zhengzhou, Henan, 450001, China
| | - Xiaoli Fu
- Department of Environmental Health, Zhengzhou University, Zhengzhou, Henan, 450001, China
| | - Bin Liu
- Department of Environmental Health, Zhengzhou University, Zhengzhou, Henan, 450001, China
| | - Xuanyin Zhang
- Department of Environmental Health, Zhengzhou University, Zhengzhou, Henan, 450001, China
| | - Fangfang Yu
- Department of Environmental Health, Zhengzhou University, Zhengzhou, Henan, 450001, China
| | - Guoyu Zhou
- Department of Environmental Health, Zhengzhou University, Zhengzhou, Henan, 450001, China
| | - Yue Ba
- Department of Environmental Health, Zhengzhou University, Zhengzhou, Henan, 450001, China.
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Lan A, Gong Y, Li X, Wang Y, Zheng D, Tang H, Wang S, Tang W, Huang C, Guan Z, Lou D. The correlation between fluoride-induced bone damage and reduced DLAV formation in Zebrafish Larvae. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2024; 288:117366. [PMID: 39561566 DOI: 10.1016/j.ecoenv.2024.117366] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/22/2024] [Revised: 11/09/2024] [Accepted: 11/15/2024] [Indexed: 11/21/2024]
Abstract
In this study, we aimed to investigate the mechanism by which fluoride exposure causes bone damage and the relationship with the loss of dorsal longitudinal anastomotic vessel (DLAV) formation in zebrafish larvae to further understanding of skeletal fluorosis. We assessed the development of chondrogenesis, osteogenesis, and DLAV angiogenesis, and reactive oxygen species (ROS) in zebrafish larvae subjected to blank control group (Con), low-fluoride group (LF), and high-fluoride group (HF). Abnormal development of the cartilage area, bone mineralization accompanied with abnormal mRNA expression of osteoblast-related OC, ALP, and Runx2b genes and osteoclast-related OPG and RANKL genes, and abnormal DLAV angiogenesis and ROS levels in zebrafish larvae were affected to varying degrees with the increase of fluoride exposure. We concluded that exposure of zebrafish embryos to fluoride can affect bone development process of chondrogenesis and osteogenesis, and that bone damage might be related to the loss of DLAV angiogenesis.
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Affiliation(s)
- Ailin Lan
- Judicial Appraisal Center, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou 550000, PR China; Key Laboratory of Forensic Toxicology of Herbal Medicines, Guizhou Education Department, Guiyang, Guizhou 550000, PR China
| | - Yi Gong
- Guiyang Healthcare Vocational University, Guiyang, Guizhou 550000, PR China
| | - Xiaofen Li
- Judicial Appraisal Center, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou 550000, PR China; Key Laboratory of Forensic Toxicology of Herbal Medicines, Guizhou Education Department, Guiyang, Guizhou 550000, PR China
| | - Yifan Wang
- Judicial Appraisal Center, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou 550000, PR China; Key Laboratory of Forensic Toxicology of Herbal Medicines, Guizhou Education Department, Guiyang, Guizhou 550000, PR China
| | - Dan Zheng
- Guiyang Matemal and Child Health Care Hospital, Guiyang, Guizhou 550000, PR China
| | - Haiming Tang
- Judicial Appraisal Center, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou 550000, PR China; Key Laboratory of Forensic Toxicology of Herbal Medicines, Guizhou Education Department, Guiyang, Guizhou 550000, PR China
| | - Siqi Wang
- Judicial Appraisal Center, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou 550000, PR China; Key Laboratory of Forensic Toxicology of Herbal Medicines, Guizhou Education Department, Guiyang, Guizhou 550000, PR China
| | - Wenchao Tang
- Key Laboratory of Forensic Toxicology of Herbal Medicines, Guizhou Education Department, Guiyang, Guizhou 550000, PR China
| | - Chunhua Huang
- Judicial Appraisal Center, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou 550000, PR China; Key Laboratory of Forensic Toxicology of Herbal Medicines, Guizhou Education Department, Guiyang, Guizhou 550000, PR China
| | - Zhizhong Guan
- Guizhou Medical University, Guiyang, Guizhou 550000, PR China.
| | - Didong Lou
- Judicial Appraisal Center, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou 550000, PR China; Key Laboratory of Forensic Toxicology of Herbal Medicines, Guizhou Education Department, Guiyang, Guizhou 550000, PR China.
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Yuan L, Sun H, Li Y, Xing Z, Yin S, Xie F, Zhou J, Li S, Wu L, Huang W, Wang T, Gao Y, Zhao L, Sun D. Fluoride Exposure from Drinking Water Increases the Risk of Stroke: An Ecological Study in Changwu Town, China. TOXICS 2024; 12:679. [PMID: 39330607 PMCID: PMC11436047 DOI: 10.3390/toxics12090679] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Revised: 09/13/2024] [Accepted: 09/16/2024] [Indexed: 09/28/2024]
Abstract
BACKGROUND Stroke is a major cause of death globally and the leading cause in China. Excessive fluoride exposure has been linked to cardiovascular conditions related to stroke risk factors such as hypertension, atherosclerosis, dyslipidemia, and cardiomyopathy. However, evidence supporting the association between fluoride exposure and stroke risk is limited. METHODS We constructed an ecological study in Changwu Town, Heilongjiang Province, China, a typical endemic fluorosis area caused by excessive fluoride exposure from drinking water. We collected demographic data, stroke prevalence, and mortality information from 2017 to 2021. Fluoride exposure data were obtained from the national monitoring project on endemic fluorosis. Water fluoride concentrations were measured using the standardized methods. Trend changes in stroke rates were assessed using annual percentage change (APC). Differences in stroke rates among fluoride exposure groups were analyzed using chi-square tests. RESULTS From 2017 to 2021, the all-ages and age-standardized stroke prevalence rates of permanent residents in Changwu Town increased year by year, while the all-ages and age-standardized mortality rates did not change significantly. The prevalence rates of stroke were significantly higher in endemic fluorosis areas compared to non-endemic areas (p < 0.001). Stratifying the population into tertile groups based on the water fluoride cumulative exposure index (WFCEI) revealed statistically significant differences in stroke prevalence rates (p < 0.001), showing a dose-response relationship with the WFCEI. However, the all-ages and age-standardized mortality rates of stroke were not found to be related to fluoride exposure. CONCLUSIONS Long-term excessive fluoride exposure from drinking water may increase the risk of stroke prevalence, indicating fluoride overexposure as a potential risk factor for stroke.
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Affiliation(s)
- Lin Yuan
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin 150081, China
- Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health of P. R. China, Harbin Medical University, Harbin 150081, China
- Heilongjiang Provincial Key Lab of Trace Elements and Human Health Harbin Medical University, Harbin 150081, China
| | - Hongna Sun
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin 150081, China
- Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health of P. R. China, Harbin Medical University, Harbin 150081, China
- Heilongjiang Provincial Key Lab of Trace Elements and Human Health Harbin Medical University, Harbin 150081, China
| | - Yue Li
- Zhaodong City Center for Disease Control and Prevention, Zhaodong 151100, China
| | - Zhifeng Xing
- Heilongjiang Provincial Center for Disease Control and Prevention, Harbin 150030, China
| | - Shihui Yin
- Heilongjiang Provincial Center for Disease Control and Prevention, Harbin 150030, China
| | - Fengyu Xie
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin 150081, China
- Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health of P. R. China, Harbin Medical University, Harbin 150081, China
- Heilongjiang Provincial Key Lab of Trace Elements and Human Health Harbin Medical University, Harbin 150081, China
| | - Jing Zhou
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin 150081, China
- Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health of P. R. China, Harbin Medical University, Harbin 150081, China
- Heilongjiang Provincial Key Lab of Trace Elements and Human Health Harbin Medical University, Harbin 150081, China
| | - Shuang Li
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin 150081, China
- Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health of P. R. China, Harbin Medical University, Harbin 150081, China
- Heilongjiang Provincial Key Lab of Trace Elements and Human Health Harbin Medical University, Harbin 150081, China
| | - Liaowei Wu
- Shaanxi Provincial People's Hospital, Xi'an 712038, China
| | - Wei Huang
- Chongqing Municipal Center for Disease Control and Prevention, Chongqing 400707, China
| | - Teng Wang
- Beilun District People's Hospital, Ningbo 315800, China
| | - Yanhui Gao
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin 150081, China
- Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health of P. R. China, Harbin Medical University, Harbin 150081, China
- Heilongjiang Provincial Key Lab of Trace Elements and Human Health Harbin Medical University, Harbin 150081, China
| | - Lijun Zhao
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin 150081, China
- Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health of P. R. China, Harbin Medical University, Harbin 150081, China
- Heilongjiang Provincial Key Lab of Trace Elements and Human Health Harbin Medical University, Harbin 150081, China
| | - Dianjun Sun
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin 150081, China
- Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health of P. R. China, Harbin Medical University, Harbin 150081, China
- Heilongjiang Provincial Key Lab of Trace Elements and Human Health Harbin Medical University, Harbin 150081, China
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7
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Montañez-Rodriguez E, Avila-Rojas SH, Jimenez-Dorantes AG, León-Contreras JC, Hernandez-Pando R, Arreola-Guerra JM, Gerarduzzi C, Meléndez-Camargo ME, Del Razo LM, Barbier OC. Morphological changes in the fetal kidney induced by exposure to fluoride during pregnancy. ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY 2024; 110:104545. [PMID: 39208996 DOI: 10.1016/j.etap.2024.104545] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Revised: 08/22/2024] [Accepted: 08/22/2024] [Indexed: 09/04/2024]
Abstract
To determine if fluoride's established negative impact on adult kidney health begins during gestation, an intergenerational model of Wistar rats was exposed to two doses of fluoride (2.5 or 5.0 mg/kg/day via gavage) 20 days before mating and during gestation (20 days). The results revealed that fluoride was distributed to the amniotic fluid and fetus, resulting in lower weight, more pronounced fetal restriction, and decreased creatinine, osmolarity, and amniotic fluid volume. At the kidney level, less development in the nephrogenic and cortical zones was observed in the fluoride treatment groups, with an imbalance in the number of glomeruli and "S" shaped bodies, an increase in the immunoexpression of the marker of proliferation Ki-67 in the nephrogenic zone, an increase in the expression of Wnt4 and more maturation of the renal tubules, indicating that fluoride exposure during pregnancy alters kidney development and promotes early maturation of tubular segments.
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Affiliation(s)
- Esaú Montañez-Rodriguez
- Department of Toxicology, Centre for Research and Advanced Studies of the National Polytechnic Institute (Cinvestav), CDMX, Mexico.
| | - Sabino Hazael Avila-Rojas
- Department of Toxicology, Centre for Research and Advanced Studies of the National Polytechnic Institute (Cinvestav), CDMX, Mexico.
| | | | | | - Rogelio Hernandez-Pando
- Experimental, National Institute of Medical Sciences and Nutrition "Salvador Zubirán,", CDMX, Mexico.
| | | | - Casimiro Gerarduzzi
- Department of Medicine, University of Montreal, Montreal, QC, Canada; Research Center, Maisonneuve-Rosemont Hospital, Montreal, QC, Canada.
| | | | - Luz M Del Razo
- Department of Toxicology, Centre for Research and Advanced Studies of the National Polytechnic Institute (Cinvestav), CDMX, Mexico.
| | - Olivier Christophe Barbier
- Department of Toxicology, Centre for Research and Advanced Studies of the National Polytechnic Institute (Cinvestav), CDMX, Mexico.
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Kumar S, Shenoy S, Swamy RS, Ravichandiran V, Kumar N. Fluoride-Induced Mitochondrial Dysfunction and Approaches for Its Intervention. Biol Trace Elem Res 2024; 202:835-849. [PMID: 37300595 DOI: 10.1007/s12011-023-03720-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2022] [Accepted: 05/28/2023] [Indexed: 06/12/2023]
Abstract
Fluoride is present everywhere in nature. The primary way that individuals are exposed to fluoride is by drinking water. It's interesting to note that while low fluoride levels are good for bone and tooth growth, prolonged fluoride exposure is bad for human health. Additionally, preclinical studies link oxidative stress, inflammation, and programmed cell death to fluoride toxicity. Moreover, mitochondria play a crucial role in the production of reactive oxygen species (ROS). On the other hand, little is known about fluoride's impact on mitophagy, biogenesis, and mitochondrial dynamics. These actions control the growth, composition, and organisation of mitochondria, and the purification of mitochondrial DNA helps to inhibit the production of reactive oxygen species and the release of cytochrome c, which enables cells to survive the effects of fluoride poisoning. In this review, we discuss the different pathways involved in mitochondrial toxicity and dysfunction induced by fluoride. For therapeutic approaches, we discussed different phytochemical and pharmacological agents which reduce the toxicity of fluoride via maintained by imbalanced cellular processes, mitochondrial dynamics, and scavenging the ROS.
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Affiliation(s)
- Sachindra Kumar
- National Institute of Pharmaceutical Education and Research, Hajipur, Industrial Area Hajipur, Vaishali, 844102, India
| | - Smita Shenoy
- Department of Pharmacology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education (MAHE), Manipal, 576104, India
| | - Ravindra Shantakumar Swamy
- Division of Anatomy, Department of Basic Medical Sciences (DBMS), Manipal Academy of Higher Education (MAHE), Manipal, 576104, India
| | - V Ravichandiran
- National Institute of Pharmaceutical Education and Research, Hajipur, Industrial Area Hajipur, Vaishali, 844102, India
| | - Nitesh Kumar
- National Institute of Pharmaceutical Education and Research, Hajipur, Industrial Area Hajipur, Vaishali, 844102, India.
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Hung M, Mohajeri A, Vu T, Moparthi H, Lipsky MS. Association between fluoride exposure and blood pressure. J Public Health Res 2023; 12:22799036231204323. [PMID: 37822995 PMCID: PMC10563487 DOI: 10.1177/22799036231204323] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2023] [Accepted: 08/22/2023] [Indexed: 10/13/2023] Open
Abstract
Objectives This study investigated whether fluoride was associated with an increased prevalence of high blood pressure (BP) among adolescents in the United States. Methods The study sample consisted of 2015-2016 National Health and Nutrition Examination Survey participants aged 13-17 years. Independent-samples t-tests, Chi-square tests, and regression models were used to analyze the data. Results A total of 814 participants met the study criteria. The findings showed that the proportion of patients with high levels of water or plasma fluoride in the high BP group was higher than that in the normal BP group. However, after adjusting for sociodemographic covariates, neither water nor plasma fluoride levels were significantly associated with a high BP. Conclusions This study did not find an association between either water or plasma fluoride levels and high BP. Further study is needed to exclude a dose dependent effect at higher levels of fluoride.
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Affiliation(s)
- Man Hung
- College of Dental Medicine, Roseman University of Health Sciences, South Jordan, UT, USA
- Division of Public Health, University of Utah, Salt Lake City, UT, USA
- Veteran Affairs Salt Lake City Health Care, Salt Lake City, UT, USA
| | - Amir Mohajeri
- College of Dental Medicine, Roseman University of Health Sciences, South Jordan, UT, USA
| | - Teresa Vu
- College of Dental Medicine, Roseman University of Health Sciences, South Jordan, UT, USA
| | - Hyma Moparthi
- College of Dental Medicine, Roseman University of Health Sciences, South Jordan, UT, USA
| | - Martin S Lipsky
- College of Dental Medicine, Roseman University of Health Sciences, South Jordan, UT, USA
- Institute on Aging, Portland State University, Portland, OR, USA
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Zhou J, Sun D, Wei W. Necessity to Pay Attention to the Effects of Low Fluoride on Human Health: an Overview of Skeletal and Non-skeletal Damages in Epidemiologic Investigations and Laboratory Studies. Biol Trace Elem Res 2023; 201:1627-1638. [PMID: 35661326 DOI: 10.1007/s12011-022-03302-7] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Accepted: 05/26/2022] [Indexed: 12/15/2022]
Abstract
Due to the implementation of water improvement and fluoride reduction plans supported by central and local governments in recent years, areas with high fluoride exposure are being gradually decreased. Therefore, it is of practical importance to study the effect of low fluoride on human health. Epidemiologic investigations and in vivo and in vitro studies based on low fluoride have also confirmed that fluoride not only causes skeletal damage, such as dental fluorosis, but also causes non-skeletal damage involving the cardiovascular system, nervous system, hepatic and renal function, reproductive system, thyroid function, blood glucose homeostasis, and the immune system. This article summarizes the effects of low fluoride on human and animal skeletal and non-skeletal systems. A preliminary exploration of corresponding mechanisms that will help to fully understand the harm of low fluoride on human health was undertaken to provide the basis for establishing new water fluoride standards and help to implement individual guidance.
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Affiliation(s)
- Jing Zhou
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, 150081, Heilongjiang Province, China
- National Health Commission, Key Laboratory of Etiology and Epidemiology, Harbin Medical University (23618504), Harbin, 150081, Heilongjiang Province, China
- Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Harbin Medical University, 150081, Harbin, Heilongjiang Province, China
| | - Dianjun Sun
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, 150081, Heilongjiang Province, China
- National Health Commission, Key Laboratory of Etiology and Epidemiology, Harbin Medical University (23618504), Harbin, 150081, Heilongjiang Province, China
- Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Harbin Medical University, 150081, Harbin, Heilongjiang Province, China
| | - Wei Wei
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, 150081, Heilongjiang Province, China.
- National Health Commission, Key Laboratory of Etiology and Epidemiology, Harbin Medical University (23618504), Harbin, 150081, Heilongjiang Province, China.
- Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Harbin Medical University, 150081, Harbin, Heilongjiang Province, China.
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11
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Wei M, Ye Y, Ali MM, Chamba Y, Tang J, Shang P. Effect of Fluoride on Cytotoxicity Involved in Mitochondrial Dysfunction: A Review of Mechanism. Front Vet Sci 2022; 9:850771. [PMID: 35518640 PMCID: PMC9062983 DOI: 10.3389/fvets.2022.850771] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2022] [Accepted: 02/07/2022] [Indexed: 12/11/2022] Open
Abstract
Fluoride is commonly found in the soil and water environment and may act as chronic poison. A large amount of fluoride deposition causes serious harm to the ecological environment and human health. Mitochondrial dysfunction is a shared feature of fluorosis, and numerous studies reported this phenomenon in different model systems. More and more evidence shows that the functions of mitochondria play an extremely influential role in the organs and tissues after fluorosis. Fluoride invades into cells and mainly damages mitochondria, resulting in decreased activity of mitochondrial related enzymes, weakening of protein expression, damage of respiratory chain, excessive fission, disturbance of fusion, disorder of calcium regulation, resulting in the decrease of intracellular ATP and the accumulation of Reactive oxygen species. At the same time, the decrease of mitochondrial membrane potential leads to the release of Cyt c, causing a series of caspase cascade reactions and resulting in apoptosis. This article mainly reviews the mechanism of cytotoxicity related to mitochondrial dysfunction after fluorosis. A series of mitochondrial dysfunction caused by fluorosis, such as mitochondrial dynamics, mitochondrial Reactive oxygen species, mitochondrial fission, mitochondrial respiratory chain, mitochondrial autophagy apoptosis, mitochondrial fusion disturbance, mitochondrial calcium regulation are emphasized, and the mechanism of the effect of fluoride on cytotoxicity related to mitochondrial dysfunction are further explored.
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Affiliation(s)
- Mingbang Wei
- College of Animal Science, Tibet Agriculture and Animal Husbandry College, Linzhi, China.,The Provincial and Ministerial Co-founded Collaborative Innovation Center for R&D in Tibet Characteristic Agricultural and Animal Husbandry Resources, Linzhi, China
| | - Yourong Ye
- College of Animal Science, Tibet Agriculture and Animal Husbandry College, Linzhi, China.,The Provincial and Ministerial Co-founded Collaborative Innovation Center for R&D in Tibet Characteristic Agricultural and Animal Husbandry Resources, Linzhi, China
| | - Muhammad Muddassir Ali
- Institute of Biochemistry and Biotechnology, University of Veterinary and Animal Sciences, Lahore, Pakistan
| | - Yangzom Chamba
- College of Animal Science, Tibet Agriculture and Animal Husbandry College, Linzhi, China.,The Provincial and Ministerial Co-founded Collaborative Innovation Center for R&D in Tibet Characteristic Agricultural and Animal Husbandry Resources, Linzhi, China
| | - Jia Tang
- College of Animal Science, Tibet Agriculture and Animal Husbandry College, Linzhi, China.,The Provincial and Ministerial Co-founded Collaborative Innovation Center for R&D in Tibet Characteristic Agricultural and Animal Husbandry Resources, Linzhi, China
| | - Peng Shang
- College of Animal Science, Tibet Agriculture and Animal Husbandry College, Linzhi, China.,The Provincial and Ministerial Co-founded Collaborative Innovation Center for R&D in Tibet Characteristic Agricultural and Animal Husbandry Resources, Linzhi, China
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12
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Ballantyne JA, Coyle G, Sarwar S, Kühn T. Fluoride Status and Cardiometabolic Health: Findings from a Representative Survey among Children and Adolescents. Nutrients 2022; 14:nu14071459. [PMID: 35406071 PMCID: PMC9003371 DOI: 10.3390/nu14071459] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Revised: 03/20/2022] [Accepted: 03/22/2022] [Indexed: 02/06/2023] Open
Abstract
There is preliminary evidence to suggest a positive association between fluoride exposure and higher blood pressure among children, but population-based biomarker studies are lacking. Thus, data from the 2013/2014 and 2015/2016 cycles of the US-based National Health and Nutrition Examination Survey (NHANES) were analysed to evaluate the association between plasma fluoride concentrations and blood pressure among children and adolescents aged 8 to 19 years. Secondary analyses were carried out on fluoride status in relation to further markers of cardio-metabolic health, i.e., anthropometric indices, biomarkers of lipid and sugar metabolism, and C-reactive protein levels. There was a positive correlation between water fluoride content and plasma fluoride concentrations (Spearman’s r = 0.41, p < 0.01). However, multivariable linear regression models did not show significant differences in adjusted mean values of systolic and diastolic blood pressure across increasing quartiles of fluoride concentrations. Further markers of cardio-metabolic health were not associated with fluoride status, with the exception of a weak inverse association between plasma fluoride and HbA1c levels. Higher plasma fluoride may not be a risk factor for increased blood pressure or impaired cardio-metabolic health among children in the USA, a non-fluoride endemic country, with wide-spread water fluoridation.
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Affiliation(s)
- Jessica A. Ballantyne
- Institute for Global Food Security (IGFS), School of Biological Sciences, Queen’s University Belfast, Belfast BT9 5DL, UK; (J.A.B.); (G.C.)
| | - Gemma Coyle
- Institute for Global Food Security (IGFS), School of Biological Sciences, Queen’s University Belfast, Belfast BT9 5DL, UK; (J.A.B.); (G.C.)
| | - Sneha Sarwar
- Institute of Nutrition and Food Sciences, University of Dhaka, Dhaka 1000, Bangladesh;
| | - Tilman Kühn
- Institute for Global Food Security (IGFS), School of Biological Sciences, Queen’s University Belfast, Belfast BT9 5DL, UK; (J.A.B.); (G.C.)
- Heidelberg Institute of Global Health (HIGH), University of Heidelberg, 69120 Heidelberg, Germany
- Correspondence: ; Tel.: +44-28-9097-1387
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