Combined Effect Of Fluoride Research Articles

Individual and combined effects of fluoride and arsenic on gut bacteria: a recent update

Individual and combined effects of fluoride and arsenic on gut bacteria: a recent update

Single and combined effect of fluoride and hardness of drinking water on nephrotoxicity: <em>in-vivo</em> study using Wistar rats as an animal model

Drinking water in areas with a high prevalence of chronic kidney disease of unknown aetiology (CKDu) in Sri Lanka is known to have high concentrations of fluoride and hardness. The present study evaluated the individual and combined effects of water hardness and fluoride on potential nephrotoxicity, using Wistar rats as an animal model. Thirty-five Wistar rats were randomly assigned into five groups (n=7). Test groups F, H, RL, and RH were given de-ionized water containing 1.5 mg/L fluoride, 200 mg/L hardness, 1.5:200 mg/L fluoride: hardness, and 5:800 mg/L fluoride: hardness respectively, while control group C was given de-ionized water. Body weight and daily water consumption were measured. Serum creatinine, urine creatinine, and urinary biomarker KIM-1 were analyzed. Histopathological changes in the kidneys were observed. There were no significant differences in body weights (p>0.05) while daily water consumption was reduced significantly in the test groups RL and RH (p<0.05). A significant increment in serum creatinine in the RL and RH groups (p<0.05), and a significant reduction in urine creatinine in the F, H, RL and RH groups (p<0.05), were recorded compared to the control. However, the highest magnitude of the effect on serum creatinine and urine creatinine was recorded in the RL group. Significant increment in KIM-1 levels were recorded in the RH group (p<0.05) while the RH group indicated a more rapid increment from the 28th day. When considering histopathology, renal tubular changes were observed in the test groups. The individual and combined effects of water hardness and fluoride may contribute to the aetiology of CKDu in Sri Lanka.

Effects of Co-exposure to Fluoride and Arsenic on TRAF-6 Signaling and NF-κB Pathway ofBoneMetabolism.

Little is known about the combined effect of fluoride (F)and arsenic (As) on bone metabolism. This study aims to explore the effect of co-exposure to F and As on the expressions of TNF receptor-associated factor 6 (TRAF-6), nuclear factor-kappa B (NF-κB), and the related factors in cell and animal experiments. With the rats exposed to different doses of F, As, and combined F-As, we found that F exposure doses were positively correlated with the protein expression of receptor activator of nuclear factor-kappa B ligand (RANKL), receptor activator of nuclear factor-kappa B (RANK), TRAF-6, NF-κB, and nuclear factor of activated T cells (NFAT-c1) (P < 0.001). As exposure doses were negatively correlated with RANK, TRAF-6, NF-κB, and NFAT-c1 (P < 0.001). The effect of F and As interaction on the protein expression of RANKL, TRAF-6, NF-κB, and NFAT-c1 was significant in bone tissue (P < 0.05). In the cellular experiment, F could promote the mRNA expression of RANK, TRAF-6, and NFAT-c1. A higher concentration of As could inhibit the mRNA expression of Tartrate-resistant acid phosphatase (TRAP), RANK, TRAF-6, and NFAT-c1. The effect of F and As interaction on the mRNA expression of TRAP, RANK, TRAF-6, and NFATc1 in osteoclasts was significant (P < 0.001). In conclusion, the expression of TRAF-6 and NF-κB pathway was affected by F and As co-exposure in osteogenic differentiation, and As could antagonize the promoting effect of F on the expression of TRAF-6, TRAP, RANKL, RANK, NF-κB, and NFAT-c1 in these exposure levels. These results could provide a scientific basis for understanding the interaction of F and As in bone formation.

Fluoride toxicity and new-onset diabetes in Finland: a hypothesis

The incidence of type 1 diabetes (T1D) has increased substantially in Finland, but the exact trigger for the onset of T1D is still unknown. We know that use of amoxicillin and anti-cariogenic fluoride tablets is a common practice for children in Finland. It seems that beta-cell destruction is initiated by modification of the proinsulin by combined effects of fluoride (F2) and amoxicillin. Amoxicillin especially when used together with clavulanic acid results in an acid environment around the beta-cells that promotes the conversion of F2 to hydrogen fluoride (HF). Unlike F2, HF can diffuse easily into the beta-cell cytosol. Because the cytosol has a neutral pH, virtually all HF reverts to F2 in the cytosol and F2 cannot easily diffuse out of the cell. Exposure to excess F2 promotes proinsulin covalent dimerization and simultaneously hyperexpression of MHC Class I molecules. Proinsulin dimers then migrate to the cell membrane with MHC class I molecules, accumulate at the beta-cell membrane and produces a powerful immunogenic stimulus for the cytotoxic T-cells. Production of cytotoxic cytokines from the infiltrating T-cells initiates the destruction of beta-cells. In Finnish children, this might be helped along by a higher beta-cell activity and by a reactive thymus-dependent immune system induced by higher levels of thyroid hormones and calcitonin respectively. After repeated similar attacks, more and more effector T-cells are raised and more and more beta-cells are destroyed, and clinical diabetes occurs.

The combined effects of fluorine and arsenic on renal function in a Chinese population

Chronic exposure to combined fluoride and arsenic continues to be a major public health problem worldwide, affecting thousands of people. The results clearly show that the combined effect of fluoride and arsenic on renal function is mainly antagonism at these exposure levels.

Chronic combined effects of fluoride and arsenite on the Runx2 and downstream related factors of bone metabolism in rats

To observe the chronic combined effects of sodium fluoride and sodium arsenite on the Runx2 and downstream related factors of bone metabolism in SD rats. SD rats were divided randomly into nine groups of 6 each by factorial experimental design (half female and half male) , and supplied with the different doses of fluoride, arsenite and fluoride plus arsenite containing in deionized water (untreated control containing 0 mg/kg fluoride and 0 mg/kg arsenite, and low-fluoride and high supplemented with 5 and 20 mg/kg fluoride, and low-arsenite and high supplemented with 2.5 and 10 mg/kg arsenite, and low-fluoride plus low-arsenite, and low-fluoride plus high-arsenite, and high-fluoride plus low-arsenite, and high-fluoride plus high-arsenite, respectively) . After 6 months exposure, the concentration of Runx2, matrix metallopeptidase 9 (MMP-9) ,Osterix, Receptor activator for nuclear factor-κ β ligand (RANKL) were detected by enzyme-linked immunosorbent assay method, respectively. There were no dental fluorosis found in the control group, low-arsenic group and high-arsenic group. There were significant differences in the constituent ratio of dental fluorosis among the rats from low-fluoride and high-fluoride (that is 5 rats out of 6 and 6 rats out of 6) compared with the control group (0 rat out of 6) (χ(2) = 8.57, 12.00, P < 0.05). The bone fluorine level increased with the increase of fluoride dose, the groups without fluoride supply (control group, low-arsenite and high-arsenite group's geometric mean (minimum-maximum) were 0.005 (0.003-0.009), 0.006 (0.003-0.021), 0.003 (0.002-0.100) mg/g, respectively), low-fluorine groups (low-fluoride group, low-fluoride plus low-arsenite, and low-fluoride plus high-arsenite group were 3.395 (2.416-5.871), 3.809 (1.471-7.799), 1.471 (1.473-6.732)mg/g, respectively) , the high-fluorine groups (high-fluoride, high-fluoride plus low-arsenite, and high-fluoride plus high-arsenite group were 70.086 (46.183-131.927), 69.925 (40.503-96.183), 40.503 (52.622-89.487) mg/g, respectively) and the differences between groups was significant (P < 0.05). The bone arsenic level increased with the increase of arsenite dose. The low-arsenic groups (low-arsenite group, low-arsenite plus low-fluoride, and low-arsenite plus high-fluoride group were 7.195 (5.060-9.860), 6.518 (2.960-12.130), 6.970 (3.400-9.730) µg/g, respectively), the high-arsenic groups (high-arsenite, high-arsenite plus low-fluoride, and high-fluoride plus high-arsenite group's geometric mean(minimum-maximum) were 8.823 (5.760-10.840), 9.470 (7.230-12.860), 8.321 (2.420-17.540) µg/g, respectively) were significantly higher than that in the groups without arsenic supply (control group, low-fluoride and high-fluoride group were 1.785 (0.300-3.750), 2.226 (1.410-3.980), 2.030 (1.040-3.850)µg/g, respectively) (P < 0.05). There was no significant difference of the bone arsenic concentration between low-arsenic and high arsenic group. There was significant positive correlation between fluoride concentration and Runx2, MMP-9, Osterix, RANKL level (the correlation coefficient was 0.647, 0.354, 0.582, 0.613 between fluorine gavage concentration and protein level, the correlation coefficient was 0.559,0.387, 0.487, 0.525 between bone fluorine concentration and protein level, respectively, P < 0.01). There was negative correlation between arsenite gavage concentration with Runx2 level (r = -0.527, P < 0.05) and was no correlation between arsenite gavage concentration with MMP-9, RANKL,Osterix level (P > 0.05). There was interaction between fluoride and arsenite to Runx2, MMP-9, RANKL,Osterix (F = 3.88, 15.66, 2.92, 6.42, respectively, P = 0.01, <0.01, 0.031, <0.01, respectively). The combined effects of fluoride and arsenic on the Runx2, MMP-9, RANKL, Osterix of bone metabolism showed antagonistic effects.

Combined effect of fluoride and 2,3,7,8-tetrachlorodibenzo-p-dioxin on mouse dental hard tissue formation in vitro

Fluoride interferes with enamel matrix secretion and mineralization and dentin mineralization. The most toxic dioxin congener, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), also impairs dental hard tissue formation and mineralization in vitro and in vivo. Our aim was to investigate in vitro whether the combined effect of sodium fluoride (NaF) and TCDD on dental hard tissue formation is potentiative. For this purpose, mandibular first and second molar tooth germs of E18 mouse embryos were cultured for 5-12days with NaF and TCDD alone at various concentrations (2.5, 5, 10, 12.5, 15, and 20μM and 5, 10, 12.5, and 15nM, respectively) to determine the highest concentrations, which alone cause no or negligible effects. Morphological changes were studied from the whole tooth photographs and histological tissue sections. The concentrations found were 15μM for NaF and 10nM for TCDD. While at these concentrations, the effects of NaF and TCDD alone were barely detectable, the effect of simultaneous exposure on dentin and enamel formation was overt; mineralization of predentin to dentin and enamel matrix secretion and mineralization were impaired. Immunohistochemical analysis revealed that the combined exposure modified amelogenin expression by odontoblasts. Morphology of ameloblasts and the expression of amelogenin indicated that ameloblasts were still secretory. The results show that NaF and TCDD have potentiative, harmful effects on the formation of dental hard tissues. Since children can be exposed to subclinical levels of fluoride and dioxins during early childhood, coincidently with mineralization of the first permanent teeth, this finding may have clinical significance.

Correlation between uncoupled ATP hydrolysis and heat production by the sarcoplasmic reticulum Ca2+-ATPase: coupling effect of fluoride.

The sarcoplasmic reticulum Ca(2+)-ATPase transports Ca(2+) using the chemical energy derived from ATP hydrolysis. Part of the chemical energy is used to translocate Ca(2+) through the membrane (work) and part is dissipated as heat. The amount of heat produced during catalysis increases after formation of the Ca(2+) gradient across the vesicle membrane. In the absence of gradient (leaky vesicles) the amount of heat produced/mol of ATP cleaved is half of that measured in the presence of the gradient. After formation of the gradient, part of the ATPase activity is not coupled to Ca(2+) transport. We now show that NaF can impair the uncoupled ATPase activity with discrete effect on the ATPase activity coupled to Ca(2+) transport. For the control vesicles not treated with NaF, after formation of the gradient only 20% of the ATP cleaved is coupled to Ca(2+) transport, and the caloric yield of the total ATPase activity (coupled plus uncoupled) is 22.8 kcal released/mol of ATP cleaved. In contrast, the vesicles treated with NaF consume only the ATP needed to maintain the gradient, and the caloric yield of ATP hydrolysis is 3.1 kcal/mol of ATP. The slow ATPase activity measured in vesicles treated with NaF has the same Ca(2+) dependence as the control vesicles. This demonstrates unambiguously that the uncoupled activity is an actual pathway of the Ca(2+)-ATPase rather than a contaminating phosphatase. We conclude that when ATP hydrolysis occurs without coupled biological work most of the chemical energy is dissipated as heat. Thus, uncoupled ATPase activity appears to be the mechanistic feature underlying the ability of the Ca(2+)-ATPase to modulated heat production.