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.

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.

Safety and Effectiveness of Copaiba Oleoresin (C. reticulata Ducke) on Inflammation and Tissue Repair of Oral Wounds in Rats.

In traditional communities of the Brazilian Amazon, the copaiba oleoresin (C. reticulata Ducke) is widely known for its therapeutic activity, especially its wound healing and anti-inflammatory actions. Our study aimed to evaluate these effects in oral lesions and the safety of the dosage proposed. A punch biopsy wound was induced on the ventral surface of the tongue of forty-five male Wistar rats under anesthesia. Animals were randomly allocated to one of three groups based on the treatment: control, corticoid and copaiba. A daily dose of each treatment and vehicle was administrated by oral gavage for three consecutive days. Sample collections took place on the third, seventh and 15th days post-wounding for clinical and histopathological analyses. Blood was collected on the third and seventh days for kidneys and liver function tests. Semi-quantitative analyses were performed based on scores of inflammation and reepithelization. Tissue collagen deposition was detected by PicroSirius red staining. Copaiba-treated wounds revealed a smaller wound area, decreased of acute inflammatory reaction and enhanced reepithelization. The levels of kidney and liver function tests did not reveal presence of damage post-treatments. Our findings suggest that copaiba oleoresin is a safe and effective alternative therapy for inflammation and tissue repair of oral wounds in this animal model.

What does scientometry tell us about mercury toxicology and its biological impairments?

Mercury is a toxic pollutant that poses risks to both human and environmental health, making it a pressing public health concern. This study aimed to summarize the knowledge on mercury toxicology and the biological impairments caused by exposure to mercury in experimental studies and/or diagnosis in humans. The research was conducted on the main collection of Web of Science, employing as a methodological tool a bibliometric analysis. The selected articles were analyzed, and extracted data such as publication year, journal, author, title, number of citations, corresponding author's country, keywords, and the knowledge mapping was performed about the type of study, chemical form of mercury, exposure period, origin of exposure, tissue/fluid of exposure measurement, mercury concentration, evaluation period (age), mercury effect, model experiments, dose, exposure pathway, and time of exposure. The selected articles were published between 1965 and 2021, with Clarkson TW being the most cited author who has also published the most articles. A total of 38% of the publications were from the USA. These studies assessed the prenatal and postnatal effects of mercury, emphasizing the impact of methylmercury on neurodevelopment, including motor and cognitive evaluations, the association between mercury and autism, and an evaluation of its protective effects against mercury toxicity. In observational studies, the blood, umbilical cord, and hair were the most frequently used for measuring mercury levels. Our data analysis reveals that mercury neurotoxicology has been extensively explored, but the association among the outcomes evaluated in experimental studies has yet to be strengthened. Providing metric evidence on what is unexplored allows for new studies that may help governmental and non-governmental organizations develop guidelines and policies.

Linalool-rich rosewood essential oil (Aniba rosaeodora Ducke) mitigates emotional and neurochemical impairments induced by ethanol binge-like exposure during adolescence in female rats.

Linalool-rich Rosewood oil (Aniba rosaeodora Ducke) is a natural compound widely used in perfumery industry. Evidence suggests that linalool exerts antidepressant and anxiolytic effects. Conversely, ethanol binge drinking (i.e., intermittent and episodic consumption) during adolescence elicits neurobehavioral alterations associated with brain damage. Here, we investigated whether linalool-rich Rosewood oil administration can improve the emotional and molecular impairments associated with ethanol binge-like exposure during adolescence in female rats. Rosewood oil was obtained by hydrodistillation and posteriorly analyzed. Adolescent female Wistar rats received four-cycles of ethanol binge-like pattern (3 g/kg/day, 3 days on/4 days off) and daily Rosewood oil (35 mg/kg, intranasally) for 28 days. Twenty-four hours after treatments, it was evaluated the impact of ethanol exposure and Rosewood oil treatment on the putative emotional impairments assessed on the splash and forced swimming tests, as well as the levels of brain-derived neurotrophic factor (BDNF), S100B, oxidative parameters, and inflammatory cytokines in prefrontal cortex and hippocampus. Results indicated that Rosewood oil intranasal administration mitigated emotional impairments induced by ethanol exposure accompanied by a marked increase in BDNF, S100B, glutathione (GSH), and antioxidant activity equivalent to Trolox (TEAC) levels in brain areas. Rosewood oil treatment also prevented the ethanol-induced increase of interleukin-1ß, interleukin-6, tumor necrosis factor α (TNF-α), and neurofilament light chain (NFL) levels. These findings provide the first evidence that Rosewood oil intranasal administration exerts protective effects against emotional and molecular impairments associated with adolescent ethanol binge-like exposure, possibly due to linalool actions triggering neurotrophic factors, rebalancing antioxidant status, and attenuating proinflammatory process.

Neurotoxicology of alcohol: a bibliometric and science mapping analysis.

Alcohol consumption is common in many societies and has increased considerably, resulting in many socioeconomic and public health problems. In this sense, studies have been carried out in order to understand the mechanisms involved in alcohol consumption and related harmful effects. This study aimed to identify and map the knowledge and to perform bibliometric analysis of the neurotoxicology of alcohol based on the 100 most cited articles. A search was carried out in the Web of Science Core Collection database and information was extracted regarding the journal, authors, keywords, year of publication, number of citations, country and continent of the corresponding author. For each selected manuscript, the study design, alcohol exposure model, dose, period of exposure, and effect on the central nervous system and research hotspots were mapped. The journal with the highest number of publications was Alcoholism: Clinical and Experimental Research (n = 11 papers), the author who contributed the most was Crews FT (n = 8 papers), the studies had a total of 288 keywords and 75% of the publications were from the United States of America. The experimental studies evaluated the effects of prenatal and postnatal exposure and were conducted in rats and mice using doses ranging from 2.5 to 14 g/kg/day, with administration by subcutaneous, intraperitoneal, intragastric, or inhalation route or with free access through drinking bottles. Among the studies mapped, the oldest one (1989) aimed to understand the systemic damage and mechanisms of action involved, while the most recent focused on understanding the receptors and mechanisms involved in addiction, as well as genetic factors. Our results show the panorama of the most widespread scientific production in the scientific community on the neurotoxicology of ethanol, a high prevalence was observed in studies that addressed fetal alcohol syndrome and/or the effects of ethanol on neurodevelopment.

Exposure to tolerable concentrations of aluminum triggers systemic and local oxidative stress and global proteomic modulation in the spinal cord of rats.

The tolerable aluminum (Al) intake levels for humans are constantly under review by regulatory agencies due to novel pre-clinical evidence on the neurotoxicity of prolonged Al exposure; however, little is known about the effects of Al on the spinal cord. This study aimed to investigate potential adverse effects on both spinal cord and systemic biochemical balance after prolonged exposure to a low dose of Al. Twenty adult rats were distributed in the control (distilled water) and exposed group (8.3 mg of AlCl3/kg/day). After 60 days, both blood and spinal cord samples were collected for oxidative stress and proteomic analyses. In plasma and erythrocytes, glutathione level was not different between groups; however, exposure to AlCl3 significantly decreased glutathione level in the spinal cord. Thiobarbituric acid reactive substances levels in the plasma and spinal cord of animals from the control group were significantly lower than those animals exposed to AlCl3. Exposure to AlCl3 significantly modulated the expression of proteins associated with the cell cycle, stimulus-response, cytoskeleton, nervous system regulation, protein activity, and synaptic signaling. Therefore, prolonged exposure to a low dose of Al triggered oxidative stress and proteomic changes that may affect spinal cord homeostasis.

Dental Caries and Salivary Oxidative Stress: Global Scientific Research Landscape.

This study aimed to analyze the research trends on salivary oxidative stress associated with dental caries and to perform bibliometric approaches for existing publications on this association. A search was performed using the Web of Science Core Collection, without any restriction of language or publication year. The number of periodicals with the most published articles in this theme, most published authors and keywords were mapped; other metrics were also evaluated such as the countries that have more research on the subject and the period in which there were more publications on the subject. During the knowledge mapping, the most frequent experimental designs were analyzed, type of saliva collection, stage of caries disease, evaluated oxidative parameters were retrieved and analyzed from each manuscript. Between the 43 selected articles, the Journal of Clinical Pediatric Dentistry was the periodical appearing the most with 4 published articles. The authors who published the most were Celec, P., Tothova, L., Hegde, A.M., Shetty, S., Antoniali, C., and Pessan, JP with three articles each, and a total of 180 keywords representing the evolution of the theme. India and Asia were found to be the country and continent with most publications, respectively. Most articles collected non-stimulated total saliva, with total antioxidant capacity being the parameter most often evaluated. The type of study that appeared the most was cross-sectional studies, and articles published in the period of 2017-2022 were the most frequent. Studies show that dental caries can be associated to the changes in salivary oxidative biochemistry with an increase in lipid peroxidation, a biomarker of oxidative damage, and an increase in antioxidant capacity in chronic caries, in response to cariogenic challenge. Some studies evidence the reduction of lipid peroxidation after treatment of the carious lesion. Our findings reveal worldwide research trends, as well as a clearer knowledge of the evolution and future scenarios of this issue, also showing the mechanisms associating dental caries with changes in salivary oxidative biochemical parameters are not clear.

Aerobic Physical Training Attenuates Oxidative Stress in the Spinal Cord of Adult Rats Induced by Binge-like Ethanol Intake.

Binge drinking is the most frequent consumption pattern among young adults and remarkably changes the central nervous system; thus, research on strategies to protect it is relevant. This study aimed to investigate the detrimental effects of binge-like EtOH intake on the spinal cord of male rats and the potential neuroprotective effects provided by moderate-intensity aerobic physical training. Male Wistar rats were distributed into the 'control group', 'training group', 'EtOH group', and 'training + EtOH'. The physical training protocol consisted of daily 30-min exercise on a treadmill for 5 consecutive days followed by 2 days off during 4 weeks. After the fifth day of each week, distilled water ('control group' and 'training group') or 3 g/kg of EtOH diluted at 20% w/v ('EtOH group' and 'training + EtOH group') was administered for 3 consecutive days through intragastric gavage to simulate compulsive consumption. Spinal cord samples were collected for oxidative biochemistry and morphometric analyses. The binge-like EtOH intake induced oxidative and tissue damage by decreasing reduced glutathione (GSH) levels, increasing lipid peroxidation (LPO), and reducing motor neurons (MN) density in the cervical segment. Even under EtOH exposure, physical training maintained GSH levels, reduced LPO, and prevented MN reduction at the cervical segment. Physical training is a non-pharmacological strategy to neuroprotect the spinal cord against oxidative damage induced by binge-like EtOH intake.

The Relationship between Exercise and Salivary Oxidative Stress: A Systematic Review.

Salivary content has been reported as a potential biomarker for oxidative stress assessments especially in context of exercise-induced oxidative stress. This systematic review following PRISMA guidelines aimed to evaluate the effects of physical exercise and changes promoted in oxidative stress identified in saliva. METHODS: Studies published up to May 2022 were searched in online databases (PubMed, Scopus, Web of Science, The Cochrane Library, LILACS, OpenGrey, and Google Scholar). Risk of bias evaluation were performed using the Quality Assessment Tool for Before-After (Pre-Post) Studies with No Control Group. RESULTS: A total of 473 references were identified and 22 considered eligible. In this case 14 studies reported increase of antioxidant parameters in saliva while eight studies demonstrated increased lipid peroxidation after exercise. Regarding nitrite levels, two studies showed higher levels after exercise. The quality of evidence was very low due to high heterogeneity, inconsistency and indirectness among studies according Grading of Recommendations, Assessment, Development and Evaluation analysis. CONCLUSION: Increase of oxidative stress and antioxidant activity in saliva appears to be present after exercise, especially at moderate intensity. However, the wide variety of methods leads to divergent data. For precision in salivary assessments, new research with larger sample sizes and better participant matching are recommended.

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.

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.

Neuroprotective Mechanisms of Resveratrol in Alzheimer's Disease: Role of SIRT1.

Alzheimer's disease (AD) is a progressive and neurodegenerative disorder of the cortex and hippocampus, which eventually leads to cognitive impairment. Although the etiology of AD remains unclear, the presence of ß-amyloid (Aß) peptides in these learning and memory regions is a hallmark of AD. Therefore, the inhibition of Aß peptide aggregation has been considered the primary therapeutic strategy for AD treatment. Many studies have shown that resveratrol has antioxidant, anti-inflammatory, and neuroprotective properties and can decrease the toxicity and aggregation of Aß peptides in the hippocampus of AD patients, promote neurogenesis, and prevent hippocampal damage. In addition, the antioxidant activity of resveratrol plays an important role in neuronal differentiation through the activation of silent information regulator-1 (SIRT1). SIRT1 plays a vital role in the growth and differentiation of neurons and prevents the apoptotic death of these neurons by deacetylating and repressing p53 activity; however, the exact mechanisms remain unclear. Resveratrol also has anti-inflammatory effects as it suppresses M1 microglia activation, which is involved in the initiation of neurodegeneration, and promotes Th2 responses by increasing anti-inflammatory cytokines and SIRT1 expression. This review will focus on the antioxidant and anti-inflammatory neuroprotective effects of resveratrol, specifically on its role in SIRT1 and the association with AD pathophysiology.