Is there any association between fluoride exposure and thyroid function modulation? A systematic review.

Numerous pre-clinical and observational studies have explored the potential effects of fluoride (F) at varying concentrations on diverse systems and organs. While some have assessed the endocrinological conditions of children and adults, a consensus regarding the interaction between F and the thyroid remains elusive. This systematic review aimed to gather primary evidence on the association between F and changes in the thyroid at optimal and high levels in water supply as stipulated by the World Health Organization. A search strategy, incorporating terms pertinent to the studies, was employed across PubMed, Scopus, Web of Science, Lilacs, and Google Scholar. Following the review of studies, data were extracted and analyzed using the Grading of Recommendations, Assessment, Development, and Evaluations to assess the quality of the evidence. Our results yielded 3,568 studies, of which seven met the inclusion criteria for this review. Five of the seven studies identified an association between high F exposure and thyroid function. In the analysis of methodological quality, every study was found to have major or minor methodological issues and significant risk of bias. The overall confidence in the evidence was deemed low for all outcomes in the seven studies. The evidence compiled in this review suggests a potential association between chronic high levels of F exposure and thyroid damage. Nonetheless, further studies with robust design and high methodological quality are required to provide evidence for policy makers and health care practitioners.

Effects of long-term fluoride exposure are associated with oxidative biochemistry impairment and global proteomic modulation, but not genotoxicity, in parotid glands of mice.

BACKGROUND: Fluoride has become widely used in dentistry because of its effectiveness in caries control. However, evidence indicates that excessive intake interferes with the metabolic processes of different tissues. Thus, this study aimed to investigate the effects of long-term exposure to F on the parotid salivary gland of mice, from the analysis of oxidative, proteomic and genotoxic parameters. MATERIALS AND METHODS: The animals received deionized water containing 0, 10 or 50 mg/L of F, as sodium fluoride, for 60 days. After, parotid glands were collected for analysis of oxidative biochemistry, global proteomic profile, genotoxicity assessment and histopathological analyses. RESULTS: The results revealed that exposure to fluoride interfered in the biochemical homeostasis of the parotid gland, with increased levels of thiobarbituric acid reactive species and reduced glutathione in the exposed groups; as well as promoted alteration of the glandular proteomic profile in these groups, especially in structural proteins and proteins related to oxidative stress. However, genotoxic assessment demonstrated that exposure to fluoride did not interfere with DNA integrity in these concentrations and durations of exposure. Also, it was not observed histopathological alterations in parotid gland. CONCLUSIONS: Thus, our results suggest that long-term exposure to fluoride promoted modulation of the proteomic and biochemical profile in the parotid glands, without inducing damage to the genetic component. These findings reinforce the importance of rationalizing the use of fluorides to maximize their preventative effects while minimizing the environmental risks.

Effects of oral appliances on serum cytokines in adults with obstructive sleep apnea: a systematic review.

PURPOSE: This review aimed to evaluate the effects of oral appliance (OA) therapy on serum inflammatory cytokines in adults diagnosed with obstructive sleep apnea (OSA). METHODS: Seven electronic databases and partial gray literature were searched without restrictions through March 2021. Articles evaluating the levels of serum inflammatory cytokines in patients with OSA after OA treatment were included. The risk of bias (RoB) was assessed using the before-and-after tool or RoB 2.0. The level of certainty was assessed using the GRADE tool. RESULTS: Five studies met the eligibility criteria. One was a randomized clinical trial (RCT), while four were non-randomized clinical trials (NRCTs). Among the studies, C-reactive protein (CRP), IL-6, IL-10, IL-1ß, and tumor necrosis factor α (TNF-α) were investigated. The RCT reported no significant differences in marker levels after 2 months of OA therapy, while the NRCTs showed improvement on CRP, TNF-α, and IL-1ß levels after longer follow-up periods. The RoB was evaluated as showing some concern in the RCT. Three NRCTs presented good RoB, and one showed a fair RoB. The level of certainty was graded as moderate quality for inflammatory marker levels assessed in the RCT The levels of certainty evaluated in NRCTs were classified as very low. CONCLUSIONS: Although limited, existing scientific evidence showed that OA therapy may improve serum cytokine levels in adults with OSA. However, short treatment periods are not effective in reducing markers of systemic inflammation which may require extended time and a decrease of in apneic events to improve.

A systematic review and meta-analysis of the association between fluoride exposure and neurological disorders.

Different studies have suggested that fluoride is related to neurological disorders in children and adolescents, but clinical evidences of which neurological parameters associated to fluoride exposure are, in fact, still controversial. In this way, this systematic review and meta-analysis aimed to show if there is an association between fluoride exposure from different sources, doses and neurological disorders. Terms related to "Humans"; "Central nervous system"; "Fluorides"; and "Neurologic manifestations" were searched in a systematic way on PubMed, Scopus, Web of Science, Lilacs, Cochrane and Google Scholar. All studies performed on humans exposed to fluoride were included on the final assessment. A meta-analysis was then performed and the quality level of evidence was performed using the GRADE approach. Our search retrieved 4,024 studies, among which 27 fulfilled the eligibility criteria. The main source of fluoride was naturally fluoridated water. Twenty-six studies showed alterations related to Intelligence Quotient (IQ) while only one has evaluated headache, insomnia, lethargy, polydipsia and polyuria. Ten studies were included on the meta-analysis, which showed IQ impairment only for individuals under high fluoride exposure considering the World Health Organization criteria, without evidences of association between low levels and any neurological disorder. However, the high heterogeneity observed compromise the final conclusions obtained by the quantitative analyses regarding such high levels. Furthermore, this association was classified as very low-level evidence. At this time, the current evidence does not allow us to state that fluoride is associated with neurological damage, indicating the need for new epidemiological studies that could provide further evidences regarding this possible association.

Lead-Induced Motor Dysfunction Is Associated with Oxidative Stress, Proteome Modulation, and Neurodegeneration in Motor Cortex of Rats.

Lead (Pb) is a toxic metal with great neurotoxic potential. The aim of this study was to investigate the effects of a long-term Pb intoxication on the global proteomic profile, oxidative biochemistry and neuronal density in motor cortex of adult rats, and the possible outcomes related to motor functions. For this, Wistar rats received for 55 days a dose of 50 mg/Kg of Pb acetate by intragastric gavage. Then, the motor abilities were evaluated by open field and inclined plane tests. To investigate the possible oxidative biochemistry modulation, the levels of pro-oxidant parameters as lipid peroxidation and nitrites were evaluated. The global proteomic profile was evaluated by ultraefficiency liquid chromatography system coupled with mass spectrometry (UPLC/MS) followed by bioinformatic analysis. Moreover, it was evaluated the mature neuron density by anti-NeuN immunostaining. The statistical analysis was performed through Student's t-test, considering p < 0.05. We observed oxidative stress triggering by the increase in malonaldehyde and nitrite levels in motor cortex. In the proteomic analysis, the motor cortex presented alterations in proteins associated with neural functioning, morphological organization, and neurodegenerative features. In addition, it was observed a decrease in the number of mature neurons. These findings, associated with previous evidences observed in spinal cord, cerebellum, and hippocampus under the same Pb administration protocol, corroborate with the motor deficits in the rats towards Pb. Thus, we conclude that the long-term administration to Pb in young Wistar rats triggers impairments at several organizational levels, such as biochemical and morphological, which resulted in poor motor performance.

Effects of Fluoride on Submandibular Glands of Mice: Changes in Oxidative Biochemistry, Proteomic Profile, and Genotoxicity.

Although fluoride (F) is well-known to prevent dental caries, changes in cell processes in different tissues have been associated with its excessive exposure. Thus, this study aimed to evaluate the effects of F exposure on biochemical, proteomic, and genotoxic parameters of submandibular glands. Twenty one old rats (n = 30) were allocated into three groups: 60 days administration of drinking water containing 10 mgF/L, 50 mgF/L, or only deionized water (control). The submandibular glands were collected for oxidative biochemistry, protein expression profile, and genotoxic potential analyses. The results showed that both F concentrations increased the levels of thiobarbituric acid-reactive substances (TBARS) and reduced glutathione (GSH) and changed the proteomic profile, mainly regarding the cytoskeleton and cellular activity. Only the exposure to 50 mgF/L induced significant changes in DNA integrity. These findings reinforce the importance of continuous monitoring of F concentration in drinking water and the need for strategies to minimize F intake from other sources to obtain maximum preventive/therapeutic effects and avoid potential adverse effects.

Long-Term Lead Exposure Since Adolescence Causes Proteomic and Morphological Alterations in the Cerebellum Associated with Motor Deficits in Adult Rats.

Lead (Pb) is an environmental contaminant that presents a high risk for human health. We aimed to investigate the possible alterations triggered by the exposure to Pb acetate for a long period in motor performance and the possible relationship with biochemical, proteomic and morphological alterations in the cerebellum of rats. Male Wistar rats were exposed for 55 days, at 50 mg/Kg of Pb acetate, and the control animals received distilled water. Open field (OF) and rotarod tests; biochemistry parameters (MDA and nitrite); staining/immunostaining of Purkinje cells (PC), mature neurons (MN), myelin sheath (MS) and synaptic vesicles (SYN) and proteomic profile were analyzed. Pb deposition on the cerebellum area and this study drove to exploratory and locomotion deficits and a decrease in the number of PC, MN, SYN and MS staining/immunostaining. The levels of MDA and nitrite remained unchanged. The proteomic profile showed alterations in proteins responsible for neurotransmitters release, as well as receptor function and second messengers signaling, and also proteins involved in the process of apoptosis. Thus, we conclude that the long-term exposure to low Pb dose promoted locomotion and histological tracings, associated with alterations in the process of cell signaling, as well as death by apoptosis.

Association Between Diabetic Retinopathy and Periodontitis-A Systematic Review.

Background: Diabetic retinopathy is a common microvascular complication in diabetic patients and is considered the main cause of visual loss worldwide. Periodontitis is a chronic inflammatory condition, which compromises dental supporting tissues. The chronic bacterial challenge in periodontitis is a persistent source of inflammatory mediators that may be associated with insulin resistance, increasing the risk of complications of diabetes mellitus. This systematic review aimed to summarize the evidence in the association between diabetic retinopathy and periodontitis. Methods: This review was registered under the number CRD 42019142267. A search strategy in five electronic databases and a gray literature source was performed based on the PECO acronym. After data extraction, the qualitative synthesis and risk of bias analyses were performed using the Newcastle-Ottawa scale. The level of evidence of all studies taken together was evaluated through the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Results: Out of the 253 citations screened, five cross-sectional studies met the eligibility criteria and were included in the qualitative analysis, in which two were judged to be of good quality, one as fair quality, and two as poor quality. Among the included studies, a significant relationship between the severity of periodontitis (CAL > 5 mm) and the severity of diabetic retinopathy (p < 0.05) was reported by four studies. Also, an association between both diseases in non-obese adults was found after adjustments [OR 2.206 (1.114-4.366); p = 0.0232). However, the analysis of evidence by GRADE assessment was rated as low. Conclusions: Although the results of individual studies suggest an association between diabetic retinopathy and periodontitis, the quality of the body of evidence was judged to be low by the GRADE approach. Further studies with larger sample sizes, adequate models of cofounders' adjustments, and prospective analysis of periodontitis and diabetes conditions ought to be conducted to clarify this association.

Chronic Exposure to Sodium Fluoride Triggers Oxidative Biochemistry Misbalance in Mice: Effects on Peripheral Blood Circulation.

The excessive fluoride (F) exposure is associated with damage to cellular processes of different tissue types, due to changes in enzymatic metabolism and breakdown of redox balance. However, few studies evaluate doses of F compatible with human consumption. Thus, this study evaluated the effects of chronic exposure to sodium fluoride (NaF) on peripheral blood of mice from the evaluation of biochemical parameters. The animals were divided into three groups (n = 10) and received three concentrations of NaF in the drinking water for 60 days: 0 mg/L F, 10 mg/L F, and 50 mg/L F. The blood was then collected for trolox equivalent antioxidant capacity (TEAC), thiobarbituric acid reactive substances (TBARS), concentrations of nitric oxide (NO), superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH). The results showed that doses of 10 mg/L F and 50 mg/L F were able to increase TBARS concentration and decrease NO levels and CAT activity in the blood, but there was no statistical difference for SOD levels. The 50 mg/L F group showed an increase in TEAC levels and a decrease in the GSH content when compared to the control group. In this way, oxidative changes in blood from chronic exposure to F, especially at the highest dose, indicate that F may be a toxic agent and, therefore, the long-term exposure to excessive doses should be avoided.

Chronic intoxication by methylmercury leads to oxidative damage and cell death in salivary glands of rats.

Methylmercury (MeHg) is one of the most toxic species of mercury, causing several systemic damages; however, its effect on the salivary glands has rarely been explored to date. This study was aimed at analyzing the mercury deposit, oxidative stress markers, and cell viability in parotid and submandibular rat salivary glands after chronic methylmercury intoxication. Herein, forty male Wistar rats (40 days old) were used in the experiment. The animals of the experimental group were intoxicated by intragastric gavage with MeHg at a dose of 0.04 mg per kg body weight per day for 35 days, whereas the control group received only corn oil, a diluent. After the period of intoxication, the glands were obtained for evaluation of total mercury deposit, cell viability, and the malondialdehyde (MDA) and the nitrite levels. Our results indicated mercury deposits in salivary glands, with a decrease in cell viability, higher levels of MDA in both glands of intoxicated animals, and a higher concentration of nitrite only in the submandibular gland of the mercury group. Thus, the intoxication by MeHg was able to generate deposits and oxidative stress in salivary glands that resulted in a decrease in cell viability in both types of glands.