Physical training minimizes immunological dysfunction, oxidative stress and tissue destruction on experimental periodontitis in rats.

The objective of this study is to investigate the effects of a moderate intensity physical training protocol, on alveolar bone morphology of rats submitted to ligature-induced periodontitis. Twenty-eight male Wistar rats were divided into four groups, considering the presence/absence of periodontitis and presence/absence of training. The training protocol was performed on a treadmill, 30 min/day, 5 days a week, for 4 weeks. In the experimental periodontal breakdown, with/without training, ligatures were placed on the lower first molars on the 14th day of the experiment, and were followed until the end of the protocol. At the end of the experiment, animals were euthanized and samples of plasma and mandibles were collected for immunoenzymatic evaluation of interleukins (IL)-1ß, IL-6, TNF-α and IL-10, evaluation of serum concentrations of C-reactive protein, analysis of lipid peroxidation (LPO) and reduced glutathione, histological and microtomographic analyses were performed. Physical training resulted in a reduced levels of IL-1ß, IL-6, TNF-α C-reactive protein and LPO and an increase in the levels of IL-10 in rats with periodontitis (p<0.05); a reduction in the inflammatory infiltrate and decreased fiber degradation was identified in histological analysis. Additionally, it was shown a decrease in vertical bone loss and an increase in the bone volume/trabecular volume ratio was identified in periodontitis+physical training group (p<0.05). Based on the results, the practice of frequent physical exercise, at moderate intensity, can contribute to the reduction of damage related to the disproportionate inflammatory response in periodontitis.

Physical training attenuates systemic cytokine response and tissue damage triggered by apical periodontitis.

Apical periodontitis (AP) is a condition characterized by inflammatory and infectious components in the tooth canal. AP affects periradicular tissues and has systemic repercussions. Physical exercise is a structured activity that requires cardiorespiratory function, and can modulate the inflammatory profile in pathological conditions. As a result, this study aimed to determine the effects of aerobic physical training (PT) on the alveolar bone with and without AP, and its systemic inflammatory repercussions. AP was induced in the mandibular first molars, and PT was performed on a treadmill for five consecutive days over four weeks, with progressive increases in speed and activity time. Blood samples were collected to determine serum cytokine levels using immunoassays, and alveolar bone samples were collected for histopathological evaluation, lesion volume and microarchitecture assessment using computed microtomography. Animals with AP had increased pro-inflammatory cytokines levels compared to those without AP; however, these levels were attenuated or restored by PT. Compared to the AP group, the AP + PT group had a smaller lesion volume and greater preservation of the bone trabeculae in the remaining alveolar bone surrounding the lesion. In overall, PT minimized the severity of AP proving to be a valid strategy for individuals undergoing endodontic treatment.

Treatment for dental erosion: a systematic review of in vitro studies.

Background: Dental erosion is a chemical loss of the mineralized dental tissue caused by exposure to nonbacterial acids. Different treatment protocols have been adopted with the use of fluoride compounds to promote the formation of a layer of mineral precipitation in eroded lesions. Aim: This systematic review aimed to evaluate the main treatments for dental erosion. Methodology: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and recorded in the Open Science Framework database (OSF) under DOI 10.17605/OSF.IO/XMFNZ. The searches were conducted in six electronic databases (Pubmed, Embase, Web of Science, Cochrane, Scopus, Lilacs) and two grey literature sources (Google Scholar and OpenGrey). The eligibility criteria included in vitro studies that evaluated eroded teeth under treatment with some topical agent. Risk of bias assessment and qualitative synthesis were performed using the Cochrane collaboration's tool for assessing risk of bias modified for in vitro studies. Results: A total of 522 studies were identified, and only four studies that fulfilled our eligibility criteria were included in this review. Among these studies, three were considered to have a low risk of bias, and one to have a high risk of bias. Two studies evaluated the anti-erosion effect of fluoride toothpaste, and the other two assessed the action of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) on the surface of human teeth. Among the products analyzed, CPP-ACP was the only one that promoted a significant increase in enamel microhardness and reduced tooth wear. Conclusion: Based on the in vitro studies included in this review, there was no anti-erosion effect after using different fluoride toothpaste. However, it should be considered that one of these studies presented a high risk of bias. On the other hand, studies with CPP-ACP showed anti-erosion efficacy when applied before or after erosive wear.

Biological Activity of Copaiba in Damage to the Alveolar Bone in a Model of Periodontitis Induced in Rats.

Several studies have investigated the effects of natural products in the treatment of diseases. Traditional Amazonian populations commonly use copaiba due to its well-known anti-inflammatory, antibacterial, and healing properties. In this study, we aimed to investigate the effects of systemic administration of copaiba oleoresin (Copaifera reticulata Ducke) on ligature-induced periodontitis in rats. To do so, 21 adult rats were divided into three groups (n = 7 each): a control group, ligature-induced periodontitis group, and ligature-induced periodontitis group treated with copaiba oleoresin (200 mg/kg/day). The ligature remained from day 0 to 14, and the copaiba oleoresin was administered via oral gavage during the last seven days. On day 14, the animals were euthanized, and mandibles were collected for histopathological evaluation and microcomputed tomography analysis. Our data showed that the administration of copaiba considerably reduced the inflammatory profile. Moreover, copaiba oleoresin limited alveolar bone loss, increased trabecular thickness and bone-to-tissue volume ratio, and decreased the number of trabeculae compared with those of the untreated experimental periodontitis group. Our findings provide pioneering evidence that supports the potential of copaiba oleoresin in reducing periodontitis-induced alveolar bone damage in rats.

Açaí (Euterpe oleracea Mart.) Attenuates Oxidative Stress and Alveolar Bone Damage in Experimental Periodontitis in Rats.

Açaí (Euterpe oleracea Mart.) juice is rich in phenolic compounds with high antioxidant capacity. It has been observed that the use of antioxidants may be an additional strategy to nonsurgical periodontal therapy as well as to prevent alveolar bone loss. Thus, the objective of this study was to investigate the effects of açaí supplementation on experimental periodontitis in rats. Twenty male Rattus norvegicus (Wistar) rats were assigned into control, açaí, experimental periodontitis, and experimental periodontitis with açaí supplementation groups. Periodontitis was induced by placing ligatures around the lower first molars. Animals in the açaí groups received 0.01 mL/g of clarified açaí juice for 14 days by intragastric gavage. At the end of the experimental period, blood was collected to assess the reduced glutathione (GSH), Trolox equivalent antioxidant capacity (TEAC), and lipid peroxidation (TBARS) levels. Moreover, hemimandibles were analyzed by micro-computed tomography (micro-CT) for alveolar bone loss and bone quality. Açaí supplementation increased blood total antioxidant capacity and decreased lipid peroxidation. It also reduced alveolar bone loss when compared to the experimental periodontitis group. Moreover, clarified açaí per se modulated the oxidative biochemistry and bone microstructure. Thus, açaí may be considered a viable alternative for managing periodontal oxidative stress and preventing alveolar bone loss.

In utero and lactational exposure to methylmercury elicits physical-chemical and morphological damages in the alveolar bone of offspring rats: The first toxicological findings.

Methylmercury (MeHg) is the most common organic form of mercury (Hg) that humans are exposed and is considered an environmental pollutant. Several populations that live in endemic regions of MeHg exposure are subject to the toxicant for long periods, including pregnant women and children, causing damage to several organs during early periods of development. Alveolar bone is an essential structure for the oral cavity, responsible for supporting teeth and masticatory forces. However, evidence on the effects of MeHg on alveolar bone and the intrauterine and lactation period is lacking. Thus, this study aimed to investigate the effects of MeHg exposure during gestation and lactation on the developing alveolar bone of offspring rats after maternal exposure. Dams were exposed during 41 days of pregnancy and lactation, and the mandibles of the offspring were collected. The alveolar bone was analyzed by Fourier Transform Infrared Spectroscopy to evaluate the physicochemical composition; by Scanning Electron Microscopy for ultrastructural evaluation; by histopathological, histochemical, and morphometric for tissue analyses. In addition, bone quality was assessed by X-ray microtomography. MeHg exposure altered the mineral composition and caused histological damage associated with a lower quantity and thickness of bone trabeculae, as well as reduced osteocyte density and collagen fiber content. A reduction in trabecular thickness and bone volume and an increase in trabecular spaces were observed and were associated with anatomical compromise of the vertical bone dimensions. Thus, the results suggest that the developing alveolar bone is susceptible to the toxic effects of MeHg when organisms are exposed during intrauterine and lactation periods. From a translational perspective, these changes in the alveolar bone can help us understand possible abnormalities induced by toxic metals and highlight the need for care for structures other than those already seen as targets for damage triggered by environmental MeHg exposure.

Fluoride exposure duringintrauterine and lactation periods promotes changes in the offspring rats' alveolar bone.

The importance of fluoride (F) for oral health is well established in the literature. However, evidence suggests that excessive exposure to this mineral is associated with adverse effects at different life stages and may affect many biological systems, especially mineralized tissues. The purpose of this study was to investigate the effects of F exposure during pregnancy and breastfeeding on the alveolar bone of the offspring since the alveolar bone is one of the supporting components of the dental elements. For this, the progeny rats were divided into three groups: control, 10 mg F/L, and 50 mg F/L for 42 (gestational and lactation periods). Analysis of the quantification of F levels in the alveolar bone by particle-induced gamma emission; Raman spectroscopy to investigate the physicochemical aspects and mineral components; computed microtomography to evaluate the alveolar bone microstructure and analyses were performed to evaluate osteocyte density and collagen quantification using polarized light microscopy. The results showed an increase in F levels in the alveolar bone, promoted changes in the chemical components in the bone of the 50 mg F/L animals (p < 0.001), and had repercussions on the microstructure of the alveolar bone, evidenced in the 10 mg F/L and 50 mg F/L groups (p < 0.001). Furthermore, F was able to modulate the content of organic bone matrix, mainly collagen; thus, this damage possibly reduced the amount of bone tissue and consequently increased the root exposure area of the exposed groups in comparison to a control group (p < 0.001). Our findings reveal that Fcan modulate the physicochemical and microstructural dimensions and reduction of alveolar bone height, increasing the exposed root region of the offspring during the prenatal and postnatal period. These findings suggest that F can modulate alveolar bone mechanical strength and force dissipation functionality.

Intrauterine and Postnatal Exposure to High Levels of Fluoride Is Associated with Motor Impairments, Oxidative Stress, and Morphological Damage in the Cerebellum of Offspring Rats.

Fluoride (F) is abundantly present on Earth and plays a beneficial role in human health. However, exposure to high doses of F can be a risk, mainly in endemic fluorosis regions. In light of this, we investigated the effects of F exposure during the intrauterine and postnatal periods of rats, in doses similar to those recommended in drinking water and the levels of F in regions with endemic fluorosis, on the offspring rats' cerebellum. Pregnant rats were divided into three groups: control (received ultrapure water only), 10 mg F/L, and 50 mg F/L for a period of 42 days (21 days gestation and 21 days lactation). At the end of the lactation period, the male pups were evaluated by behavioral tests, morphological markers, and biochemistry assays. The results pointed out that 50 mg F/L exposure during the intrauterine and lactational period of rats is capable of promoting oxidative stress in the cerebellum with a decrease in Purkinje cell density and myelin basic protein compromise, which could be associated with functional motor impairments. In addition, although 10 mg F/L exposure promoted redox alterations, it did not affect other parameters evaluated, highlighting the safe use of F in low doses.

Maternal Fluoride Exposure Exerts Different Toxicity Patterns in Parotid and Submandibular Glands of Offspring Rats.

There is currently a controversial and heated debate about the safety and ethical aspects of fluoride (F) used for human consumption. Thus, this study assessed the effects of prenatal and postnatal F exposure of rats on the salivary glands of their offspring. Pregnant rats were exposed to 0, 10, or 50 mg F/L from the drinking water, from the first day of gestation until offspring weaning (42 days). The offspring rats were euthanized for the collection of the parotid (PA) and submandibular (SM) glands, to assess the oxidative biochemistry and to perform morphometric and immunohistochemical analyses. F exposure was associated with a decrease in the antioxidant competence of PA in the 10 mg F/L group, contrasting with the increase observed in the 50 mg F/L group. On the other hand, the antioxidant competence of the SM glands was decreased at both concentrations. Moreover, both 10 and 50 mg F/L groups showed lower anti-α-smooth muscle actin immunostaining area in SM, while exposure to 50 mg F/L was associated with changes in gland morphometry by increasing the duct area in both glands. These findings demonstrate a greater susceptibility of the SM glands of the offspring to F at high concentration in comparison to PA, reinforcing the need to adhere to the optimum F levels recommended by the regulatory agencies. Such findings must be interpreted with caution, especially considering their translational meaning.

Salivary Glands after Prolonged Aluminum Exposure: Proteomic Approach Underlying Biochemical and Morphological Impairments in Rats.

Aluminum (Al) is one of the most abundant elements on Earth, and its high extraction rate and industrial use make human exposure very common. As Al may be a human toxicant, it is important to investigate the effects of Al exposure, mainly at low doses and for prolonged periods, by simulating human exposure. This work aimed to study the effects of low-dose exposure to chloride aluminum (AlCl3) on the oxidative biochemistry, proteomic profile, and morphology of the major salivary glands. Wistar male rats were exposed to 8.3 mg/kg/day of AlCl3 via intragastric gavage for 60 days. Then, the parotid and submandibular glands were subjected to biochemical assays, proteomic evaluation, and histological analysis. Al caused oxidative imbalance in both salivary glands. Dysregulation of protein expression, mainly of those related to cytoarchitecture, energy metabolism and glandular function, was detected in both salivary glands. Al also promoted histological alterations, such as acinar atrophy and an increase in parenchymal tissue. Prolonged exposure to Al, even at low doses, was able to modulate molecular alterations associated with morphological impairments in the salivary glands of rats. From this perspective, prolonged Al exposure may be a risk to exposed populations and their oral health.

What Is Known about Midazolam? A Bibliometric Approach of the Literature.

Midazolam is a drug with actions towards the central nervous system producing sedative and anticonvulsants effects, used for sedation and seizures treatments. A better understanding about its effects in the different scenarios presented in the literature could be helpful to gather information regarding its clinical indications, pharmacological interactions, and adverse events. From this perspective, the aim of this study was to analyze the global research about midazolam mapping, specifically the knowledge of the 100 most-cited papers about this research field. For this, a search was executed on the Web of Science-Core Collection database using bibliometric methodological tools. The search strategy retrieved 34,799 articles. A total of 170 articles were evaluated, with 70 articles being excluded for not meeting the inclusion criteria. The 100 most-cited articles rendered 42,480 citations on WoS-CC, ranging from 253 to 1744. Non-systematic review was the most published study type, mainly from North America, during the period of 1992 to 2002. The most frequent keywords were midazolam and pharmacokinetics. Regarding the authors, Thummel and Kunze were the ones with the greatest number of papers included. Our findings showed the global research trends about midazolam, mainly related to its different effects and uses throughout the time.

Long-term exposure to low doses of aluminum affects mineral content and microarchitecture of rats alveolar bone.

Aluminum (Al) is one of the most found elements in nature in many forms, and human exposure can be quite common. Therefore, it is important to investigate the effects of exposure to Al mainly at low doses and for a prolonged period, in order to simulate human exposure in the periodontium, an important structure for support and protection of the teeth. This investigation aimed to study the aluminum chloride (AlCl3) toxicological effects in the mineral composition and micromorphology of the alveolar bone of rats. Two groups of eight male Wistar rats were used for the experiment. AlCl3 group was exposed to AlCl3 orally at a dose of 8.3 mg/kg/day for 60 days, while the control group received only distilled water. After that, the mandibles were collected and submitted to the following analyses: Fourier transform infrared spectroscopy, Raman spectroscopy, and X-ray microtomography analysis; blood was also collected for determination of Al circulating levels. Our data showed that AlCl3 was capable of increasing Al circulating levels in blood. It was able to promote changes in the mineral content and triggers significant changes in the mineralized bone microstructure, such as number and thickness of trabeculae, being associated with alveolar bone-loss.

Binge-Like Exposure During Adolescence Induces Detrimental Effects in Alveolar Bone that Persist in Adulthood.

BACKGROUND: Alcohol (EtOH) intake during adolescence has become an important public health issue. Although the detrimental effects of EtOH intake on the musculoskeletal system are well known, only a few studies have investigated its impact on the stomatognathic system of adolescents. This study aimed to investigate the effect of EtOH binge drinking on the alveolar bone and the long-term consequences after abstinence. METHODS: Adolescent female Wistar rats (35 days old) were exposed to 4 cycles of EtOH binge drinking (3 g/kg/d; 3 days On-4 days Off) or distilled water (control group). Alveolar bone micromorphology and vertical bone distance were evaluated at 1, 30, and 60 days after that last EtOH intake through X-ray computed microtomography. The mineral:matrix ratio was assessed through Raman spectroscopy. RESULTS: A decrease in both trabecular thickness and volume ratio, and an increase in trabecular separation were observed at the 1-day evaluation (immediate withdrawal). After 30 and 60 days, the alveolar bone parameters were found similar to control, except for the mineral:matrix ratio in the long-term abstinence. CONCLUSIONS: EtOH binge drinking during adolescence results in alveolar bone damage that may persist in adulthood, even after abstinence.

Prolonged caffeine intake decreases alveolar bone damage induced by binge-like ethanol consumption in adolescent female rats.

Ethanol consumption has been reported to negatively impact on periodontal disease. In particular, oral cavity disorders occur upon ethanol exposure during adolescence, a life period associated with particular patterns of short and intense ('binge-like') ethanol consumption that is most deleterious to oral health. The hazardous central effects of ethanol have been linked to the overfunction of adenosine receptors, which are antagonized by caffeine, a bioactive substance present in numerous natural nutrients, which can also modify bone metabolism. The aim of this study was to investigate the effects of caffeine on alveolar bone damage induced by an ethanol binge drinking paradigm during adolescence. Female Wistar rats (35 days old; n = 30) were allocated to six groups: control (vehicle), ethanol (3 g/kg/day; 3 days On-4 days Off challenge), caffeine (10 mg/kg/day), caffeine plus ethanol, SCH58261 (0.1 mg/kg/day, an antagonist of A2A receptors), and SCH58261 plus ethanol. Bone micromorphology and vertical bone loss were analyzed by computed microtomography. Our data showed that ethanol binge drinking reduced alveolar bone quality, with repercussion on alveolar bone size. This ethanol-induced alveolar bone deterioration was abrogated upon treatment with caffeine, but not with SCH58261. This shows that caffeine prevented the periodontal disorder caused by ethanol binge drinking during adolescence, an effect that was not mediated by adenosine A2A receptor blockade.

Ethanol binge drinking exposure affects alveolar bone quality and aggravates bone loss in experimentally-induced periodontitis.

BACKGROUND: Periodontitis is a multifactorial inflammatory disease of tooth supporting tissues caused by oral biofilms, influenced by environmental and genetic factors, among others. Ethanol consumption has been considered a factor that enhances alveolar bone loss, especially in high doses. The present study aims to investigate the changes promoted by ethanol binge drinking per se or associated with ligature-induced periodontal breakdown on alveolar bone loss. MATERIALS AND METHODS: Thirty-two Wistar rats were randomly allocated into four groups: control (C), ethanol (3g/kg/day; 3 days On-4 days Off protocol by gavage for 28 days, EtOH), experimental periodontitis (EP) and experimental periodontitis plus ethanol administration (EP+EtOH). On day 14th, periodontitis was induced by ligatures that were placed around the lower first molars. On day 28th, the animals were euthanized and mandibles were submitted to stereomicroscopy for exposed root area analysis and micro-computed tomography (micro-CT) for the evaluation of alveolar bone loss and microstructural parameters. RESULTS: The results revealed that ligature-induced alveolar bone loss is aggravated by ethanol binge drinking compared to controls (1.06 ± 0.10 vs 0.77 ± 0.04; p<0.0001). In addition, binge drinking per se altered the alveolar bone quality and density demonstrating a reduction in trabecular thickness, trabecular number parameter and bone density percentual. Periodontal disorder plus ethanol binge drinking group also demonstrated reduction of the quality of bone measured by trabecular thickness. CONCLUSIONS: In conclusion, intense and episodic ethanol intake decreased alveolar bone quality in all microstructural parameters analyzed which may be considered a modifying factor of periodontitis, intensifying the already installed disease.

Blood Oxidative Stress Modulates Alveolar Bone Loss in Chronically Stressed Rats.

We aimed to investigate the effects of chronic stress (CS) on experimental periodontitis (EP) in rats. For this, 28 Wistar rats were divided into four groups: control, ligature-induced experimental periodontitis (EP), chronic stress (CS; by physical restraint model) and CS+EP (association of chronic stress and ligature-induced periodontitis). The experimental period lasted 30 days, including exposure to CS every day and ligature was performed on the 15th experimental day. After 30 days, the animals were submitted to the behavioral test of the elevated plus maze (EPM). Next, rats were euthanized for blood and mandible collection in order to evaluate the oxidative biochemistry (by nitric oxide (NO), reduced-glutathione activity (GSH), and thiobarbituric acid reactive substance levels (TBARS)) and alveolar bone characterization (by morphometric, micro-CT, and immunohistochemistry), respectively. The behavioral parameters evaluated in EPM indicated higher anxiogenic activity in the CS and CS+EP, groups, which is a behavioral reflex of CS. The results showed that CS was able to change the blood oxidative biochemistry in CS and CS+EP groups, decrease GSH activity in the blood, and increase the NO and TBARS concentrations. Thus, CS induces oxidative blood imbalance, which can potentialize or generate morphological, structural, and metabolic damages to the alveolar bone.

Aluminum-Induced Toxicity in Salivary Glands of Mice After Long-term Exposure: Insights into the Redox State and Morphological Analyses.

Several studies indicate aluminum (Al) as a potent toxicant, mainly related to central nervous system disorders. However, investigations about the Al effects over salivary glands are still scarce. In this way, the present study aimed to investigate whether the Al chloride (AlCl3) is able of triggering oxidative stress in parotid and submandibular glands of mice and also, if any morphological impairment is observed. For this, twenty mice were divided into two groups: Exposed group (EG), which received 18.5 mg/kg of AlCl3 by intragastric gavage for 60 days and control group (CG), which received distilled water by intragastric gavage during the same period of time. After that, levels of reduced glutathione (GSH) and malonaldehyde (MDA) were analyzed and we performed morphological analyses by evaluating the area of parenchyma, stroma, acini, and ducts in both glands. Statistical analyses were performed by Student's t test and two-way ANOVA, adopting p < 0.05. No abnormal body weight was observed and data indicates that although both major salivary glands are susceptible to Al-induced oxidative stress, by increasing MDA and reducing GSH, only submandibular glands decreased the parenchyma and increased stroma area. Moreover, the submandibular glands showed smaller total area of acini and higher total area of ducts, in comparison with the control group. Notably, AlCl3 induces oxidative stress in both glands, however, submandibular glands showed to be more susceptible to Al effects than parotid glands. Our study gives evidences about Al toxicity in parotid and submandibular glands and claims for new investigations to understand more mechanisms of Al-induced toxicity.