Publications by authors named "Leonardo Oliveira Bittencourt"

35 Publications

Non-Lethal Concentration of MeHg Causes Marked Responses in the DNA Repair, Integrity, and Replication Pathways in the Exposed Human Salivary Gland Cell Line.

Front Pharmacol 2021 25;12:698671. Epub 2021 Aug 25.

Laboratory of Functional and Structural Biology, Federal University of Pará, Belém, Brazil.

In Brazilian northern Amazon, communities are potentially exposed and vulnerable to methylmercury (MeHg) toxicity through the vast ingestion of fish. and studies demonstrated that the salivary glands as a susceptible organ to this potent environmental pollutant, reporting alterations on physiological, biochemical, and proteomic parameters. However, the alterations caused by MeHg on the gene expression of the exposed human salivary gland cells are still unknown. Therefore, the goal was to perform the transcriptome profile of the human salivary gland cell line after exposure to MeHg, using the microarray technique and posterior bioinformatics analysis. The cell exposure was performed using 2.5 µM MeHg. A previously published study demonstrated that this concentration belongs to a range of concentrations that caused biochemical and metabolic alterations in this linage. As a result, the MeHg exposure did not cause lethality in the human salivary gland cells line but was able to alter the expression of 155 genes. Downregulated genes (15) are entirety relating to the cell metabolism impairment, and according to KEGG analysis, they belong to the glycosphingolipid (GSL) biosynthesis pathway. On the other hand, most of the 140 upregulated genes were related to cell-cycle progression, DNA repair, and replication pathway, or cellular defenses through the GSH basal metabolism. These genomic changes revealed the effort to the cell to maintain physiological and genomic stability to avoid cell death, being in accordance with the nonlethality in the toxicity test. Last, the results support in-depth studies on nonlethal MeHg concentrations for biomarkers identification that interpret transcriptomics data in toxicological tests serving as an early alert of physiological changes biological models.
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http://dx.doi.org/10.3389/fphar.2021.698671DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8423918PMC
August 2021

Salivary parameters alterations after early exposure to environmental methylmercury: A preclinical study in offspring rats.

J Trace Elem Med Biol 2021 Jul 16;68:126820. Epub 2021 Jul 16.

Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Para, Belém, PA, Brazil. Electronic address:

Background: Methylmercury (MeHg) is still considered a global pollutant of major concern; thus, it becomes relevant to investigate and validate alternative diagnostic methods to track early-life human exposure. This study aimed to evaluate the salivary parameters and to characterize potential mechanisms of oxidative damage on the salivary glands (SG) of offspring rats after pre- and postnatal environmental-experimental MeHg exposure.

Methods: Pregnant Wistar rats were daily exposed to 40 μg/kg MeHg during both gestational and lactation periods. Then, the saliva of offspring rats was analyzed in terms of flow rate, amylase activity, and total protein concentration. The SG of the offspring rats were dissected to perform the oxidative biochemistry analyses of antioxidant capacity against peroxyl radicals (ACAP), lipid peroxidation (LPO), and nitrite levels.

Results: Exposure to MeHg significantly decreased the ACAP, increased LPO and nitrite levels, decreased salivary flow rate, amylase activity, and total protein concentration.

Conclusion: Saliva analyses can predict damages induced by early-life MeHg exposure and may be used as an auxiliary diagnostic method.
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http://dx.doi.org/10.1016/j.jtemb.2021.126820DOI Listing
July 2021

Methylmercury-induced cytotoxicity and oxidative biochemistry impairment in dental pulp stem cells: the first toxicological findings.

PeerJ 2021 10;9:e11114. Epub 2021 Jun 10.

Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará (UFPA), Belém, Pará, Brazil, Brazil.

Background: Methylmercury (MeHg) is a potent toxicant able to harm human health, and its main route of contamination is associated with the consumption of contaminated fish and other seafood. Moreover, dental amalgams are also associated with mercury release on human saliva and may contribute to the accumulation of systemic mercury. In this way, the oral cavity seems to be the primary location of exposure during MeHg contaminated food ingestion and dental procedures but there is a lack of literature about its effects on dental tissues and the impact of this toxicity on human health. In this way, this study aimed to analyze the effects of different doses of MeHg on human dental pulp stem cells after short-term exposure.

Methods: Dental pulp stem cells from human exfoliated deciduous teeth (SHED) were treated with 0.1, 2.5 and 5 µM of MeHg during 24 h. The MeHg effects were assessed by evaluating cell viability with Trypan blue exclusion assay. The metabolic viability was indirectly assessed by MTT reduction assay. In order to evaluate an indicative of antioxidant defense impairment, cells exposed to 0.1 and 5 µM MeHg were tested by measuring glutathione (GSH) level.

Results: It was observed that cell viability decreased significantly after exposure to 2.5 and 5 µM of MeHg, but the metabolic viability only decreased significantly at 5 µM MeHg exposure, accompanied by a significant decrease in GSH levels. These results suggest that an acute exposure of MeHg in concentrations higher than 2.5 µM has cytotoxic effects and reduction of antioxidant capacity on dental pulp stem cells.
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http://dx.doi.org/10.7717/peerj.11114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199917PMC
June 2021

Gene Expression Profile in Immortalized Human Periodontal Ligament Fibroblasts Through hTERT Ectopic Expression: Transcriptome and Bioinformatic Analysis.

Front Mol Biosci 2021 1;8:679548. Epub 2021 Jun 1.

Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará, Belém, Brazil.

Human periodontal ligament fibroblast (hPLF) cells play an important role in maintaining oral cavity homeostasis with special function in tissue regeneration and maintenance of dental alveoli. Although their primary cell cultures are considered a good experimental model with no genetic changes, the finite life span may limit some experimental designs. The immortalization process increases cell life span but may cause genetic changes and chromosomal instability, resulting in direct effects on physiological cell responses. In this way, we aimed to investigate the global gene expression of hPLFs after the immortalization process by the ectopic expression of the catalytic subunit of the enzyme telomerase reverse transcriptase (hTERT) through transcriptome analysis. The embryonic origin of the primary culture of hPLF cells and immortalized hPLF-hTERT was also tested by vimentin staining, hTERT synthesis evaluated by indirect immunocytochemistry, analysis of cell proliferation, and morphology. The results indicated that hPLFs and hPLF-hTERT were positive for vimentin. On the 20th cell passage, hPLFs were in senescence, while hPLF-hTERT maintained their proliferation and morphology characteristics. At the same passage, hPLF-hTERT presented a significant increase in hTERT synthesis, but transcriptome did not reveal overexpression of the hTERT gene. Fifty-eight genes had their expression altered (11 upregulated and 47 downregulated) with the absence of changes in the key genes related to these cell types and in the main cancer-associated genes. In addition, the increase in hTERT protein expression without the overexpression of its gene indicates posttranscriptional level regulation. Successful immortalization of hPLFs through the ectopic expression of hTERT encourages further studies to design experimental protocols to investigate clinical questions from a translational perspective.
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http://dx.doi.org/10.3389/fmolb.2021.679548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204186PMC
June 2021

Human cultured IMR-32 neuronal-like and U87 glial-like cells have different patterns of toxicity under fluoride exposure.

PLoS One 2021 17;16(6):e0251200. Epub 2021 Jun 17.

Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará, Belém, Brazil.

Background: Fluoride (F) is a naturally exists in nature but several studies have indicated it as an environmental toxicant to all leaving beings. Human F exposure has increased over the years since this ion has been used by industry on foods, beverages, toothpastes and on water supply. Although F is safe at optimal concentrations in water supply, human exposure to high levels could trigger neurofunctional deficits.

Materials And Methods: In this study, human glial-like (U87) and neuronal-like (IMR-32) cells lineages were used to access F toxicity and CNS cell sensibility on both cell facing the same protocol. Cells were exposed to F over 3, 5 and 10 days on two different F concentrations. Fluoride exposed cells were evaluated by standard toxicity assays to cell viability, apoptosis, necrosis and general cell metabolism. Oxidative stress parameters were evaluated by ATP and ROS levels, lipid peroxidation, GSH/GSSG ratio and comet assay.

Results: No changes were observed in IMR-32 at any given time while after 10 days of exposure to 0.22μg/mL, U87 glial-like cells showed signs of toxicity such as decreased cell viability by necrosis while general cell metabolism was increased. Oxidative stress parameters were next evaluated only on U87 glial-like cells after 10 days of exposure. F induced a decrease on ATP levels while no changes were observed on reactive oxygen species and lipid peroxidation. GSH/GSSG ratio was decreased followed by DNA damage both on 0.22μg/mL F.

Conclusions: Our results suggest an important differential behavior of the distinct types of cells exposed to the different fluoride concentrations, pointing that the U87 glial-like cells as more susceptible to damage triggered by this ion.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251200PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211231PMC
June 2021

Is There Any Association Between Neurodegenerative Diseases and Periodontitis? A Systematic Review.

Front Aging Neurosci 2021 24;13:651437. Epub 2021 May 24.

Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará, Belém, Brazil.

Neurodegenerative diseases are a group of progressive disorders that affect the central nervous system (CNS) such as Alzheimer, Parkinson, and multiple sclerosis. Inflammation plays a critical role in the onset and progression of these injuries. Periodontitis is considered an inflammatory disease caused by oral biofilms around the tooth-supporting tissues, leading to a systemic and chronic inflammatory condition. Thus, this systematic review aimed to search for evidence in the association between neurodegenerative disorders and periodontitis. This systematic review was registered at International Prospective Register of Systematic Reviews (PROSPERO) under the code CRD 42016038327. The search strategy was performed in three electronic databases and one gray literature source-PubMed, Scopus, Web of Science, and OpenGrey, based on the PECO acronym: observational studies in humans (P) in which a neurodegenerative disease was present (E) or absent (C) to observe an association with periodontitis (O). The Fowkes and Fulton checklist was used to critically appraise the methodological quality and the risk of bias of individual studies. The quality of evidence was assessed by the Grading of Recommendations Assessment, Development and Evaluation (GRADE). From 534 articles found, 12 were included, of which eight were case-control, three were cross-sectional, and one was a cohort, giving a total of 3,460 participants. All the included studies reported an association between some neurodegenerative diseases and periodontitis and presented a low risk of bias. According to the GRADE approach, the level of evidence of probing pocket depth was considered very low due to the significant heterogeneity across the studies' upgrading imprecision and inconsistency. Although all the included studies in this review reported an association between neurodegenerative diseases and periodontitis, the level of evidence was classified to be very low, which suggests a cautious interpretation of the results.
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http://dx.doi.org/10.3389/fnagi.2021.651437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180549PMC
May 2021

Metabolic and oxidative impairments in human salivary gland cells line exposed to MeHg.

J Trace Elem Med Biol 2021 Jul 18;66:126747. Epub 2021 Mar 18.

Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará, Belém, PA, Brazil. Electronic address:

Background/aim: The ingestion of contaminated seafood by MeHg is considered the main route of human exposure, turning the salivary gland one important target organ. The salivary glands play critical roles in maintaining oral health homeostasis, producing saliva that maintains the oral microbiota, initiation of the digestion of macromolecules, and being essential in maintaining the integrity of the adjacent soft tissues and teeth. Thus, this study aimed to investigate the effects of MeHg exposure on human salivary gland cells line.

Methods: Cells were exposed to 1-6 μM of MeHg for 24 h, and analysis of toxicity was performed. Based on these results, the LC50 was calculated and two concentrations were chosen (0.25 and 2.5 μM MeHg) to evaluate intracellular mercury (Hg) accumulation (THg), metabolic viability and oxidative stress parameters (GSH:GSSG ratio, lipid peroxidation, protein oxidation and DNA damage).

Results: The results demonstrated accumulation of THg as we increased the MeHg concentrations in the exposure and, the higher the dose, the lower is the cell metabolic response. In addition, the 2.5 μM MeHg concentration also triggered oxidative stress in human salivary gland cells by depleting the antioxidant competence of GSH:GSSG ratio and increasing lipid peroxidation and proteins carbonyl levels, but no damages to DNA integrity.

Conclusion: In conclusion, although these two elected doses did not show lethal effects, the highest dose triggered oxidative stress and new questionings about long-term exposure models are raised to investigate furthers cellular damages to human salivary gland cells caused by MeHg exposure to extrapolate in a translational perspective.
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http://dx.doi.org/10.1016/j.jtemb.2021.126747DOI Listing
July 2021

Imaging Microstructural Damage and Alveolar Bone Loss in Rats Systemically Exposed to Methylmercury: First Experimental Evidence.

Biol Trace Elem Res 2021 Oct 6;199(10):3707-3717. Epub 2021 Jan 6.

Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará, Augusto Corrêa Street N. 01, Guamá, Belém, Pará, 66075-110, Brazil.

The alveolar bone is an important mineralized structure of the periodontal support apparatus, and information about the methylmercury (MeHg) effects on the structural integrity is scarce. Therefore, this study aimed to investigate whether systemic, chronic, and low-dose exposure to MeHg can change the alveolar bone microstructure of rats. Adult Wistar rats (n = 30) were exposed to 0.04 mg/kg/day of MeHg or vehicle through intragastric gavage. The animals were euthanized after 60 days, and blood samples were collected for trolox equivalent antioxidant capacity (TEAC), glutathione (GSH), lipid peroxidation (LPO), and comet assays. The mandible of each animal was collected and separated into hemimandibles that were used to determine the total Hg level in the bone and to analyze microstructural damage and alveolar bone loss in terms of trabecular number (Tb.N), trabecular thickness (Tb.Th), bone volume fraction (BV/TV), and exposed root area of the second molars. MeHg exposure triggered oxidative stress in blood represented by lower levels of GSH and TEAC and the increase in LPO and DNA damage of the blood cells. High total Hg levels were found in the alveolar bone, and the microstructural analyses showed a reduction in Tb.N, Tb.Th, and BV/TV, which resulted in an increase in the exposed root area and a decrease in bone height. Long-term MeHg exposure promotes a systemic redox imbalance associated with microstructural changes and alveolar bone loss and may indicate a potential risk indicator for periodontal diseases.
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http://dx.doi.org/10.1007/s12011-020-02492-2DOI Listing
October 2021

Effects of Chronic Ethanol Consumption and Ovariectomy on the Spontaneous Alveolar Bone Loss in Rats.

Int J Dent 2020 12;2020:8873462. Epub 2020 Nov 12.

Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará, Belém-Pará 66075-110, Brazil.

Postmenopausal estrogen deficiency and ethanol (EtOH) abuse are known risk factors for different diseases including bone tissues. However, little is known about the synergic effects of EtOH abuse and estrogen deficiency on alveolar bone loss in women. The present study evaluated the effects of EtOH chronic exposure and ovariectomy on the alveolar bone loss in female rats. For this, 40 female Wistar rats were randomly divided into 4 groups: control, EtOH exposure, ovariectomy (OVX), and OVX plus EtOH exposure. Initially, half of the animals were ovariectomized at 75 days of age. After that, the groups received distilled water or EtOH 6.5 g/kg/day (20% w/v) for 55 days via gavage. Thereafter, animals were sacrificed and the mandibles were collected, dissected, and separated into hemimandibles. Alveolar bone loss was evaluated by measuring the distance between the cementoenamel junction and the alveolar bone crest through a stereomicroscope in 3 different anatomical regions of the tissue. One-way ANOVA and post hoc Tukey were used to compare groups ( < 0.05). The results showed that the ovariectomy and EtOH exposure per se were able to induce alveolar bone loss, and their association did intensify significantly the effect. Therefore, OVX associated with heavy EtOH exposure increase the spontaneous alveolar bone loss in rats.
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http://dx.doi.org/10.1155/2020/8873462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7676921PMC
November 2020

Effects of lead exposure on salivary glands of rats: insights into the oxidative biochemistry and glandular morphology.

Environ Sci Pollut Res Int 2021 Mar 26;28(9):10918-10930. Epub 2020 Oct 26.

Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará, Augusto Corrêa Street, Guamá, Belém, PA, 66075-110, Brazil.

This study aimed to investigate the effects of lead (Pb) exposure on parotid and submandibular glands through morphological aspects as well as the systemic and salivary gland redox state. Male Wistar rats were exposed to 50 mg/kg/day of Pb-acetate or distilled water by intragastric gavage for 55 days (n = 40). Blood samples were used for lipid peroxidation (LPO), glutathione (GSH), and trolox equivalent antioxidant capacity (TEAC) assays. Samples of salivary glands were analyzed by LPO, nitrites (NO), and antioxidant capacity against peroxyl radicals (ACAP) levels. Morphometric analyses (total stromal area [TSA], total parenchyma area [TPA], total ductal area [TDA], and total acinar area [TAA]) and immunohistochemistry for cytokeratin-19 (CK-19), metallothionein I/II (MT I/II), and anti-smooth muscle actin (α-SMA) were performed. The results revealed that exposure to Pb triggered systemic oxidative stress represented by lower GSH levels and increased TBARS/TEAC ratio in blood plasma. ACAP was reduced, while NO and LPO were increased in both parotid and submandibular. The morphological analyses showed increase on MT I/II expression, reduced CK-19 expression in both glands, and α-SMA reduced the immunostaining only in the parotid glands. The morphometric analyses revealed an increase in TPA in both glands, while TAA was reduced only in submandibular glands and TDA was increased only in parotid glands. Our findings are pioneer in showing that long-term exposure to Pb is able to promote blood and glandular oxidative stress associated with cellular, morphological, and biochemical damage in both parotid and submandibular glands.
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http://dx.doi.org/10.1007/s11356-020-11270-5DOI Listing
March 2021

Fluoride exposure during pregnancy and lactation triggers oxidative stress and molecular changes in hippocampus of offspring rats.

Ecotoxicol Environ Saf 2021 Jan 20;208:111437. Epub 2020 Oct 20.

Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará, Belém, Brazil. Electronic address:

Long-term exposure to high concentrations of fluoride (F) can damage mineralized and soft tissues such as bones, liver, kidney, intestine, and nervous system of adult rats. The high permeability of the blood-brain barrier and placenta to F during pregnancy and lactation may be critical to neurological development. Therefore, this study aimed to investigate the effects of F exposure during pregnancy and lactation on molecular processes and oxidative biochemistry of offspring rats' hippocampus. Pregnant Wistar rats were randomly assigned into 3 groups in accordance with the drinking water received: G1 - deionized water (control); G2 - 10 mg/L of F and G3 - 50 mg/L of F. The exposure to fluoridated water began on the first day of pregnancy and lasted until the 21 day of breastfeeding (when the offspring rats were weaned). Blood plasma samples of the offspring rats were collected to determine F levels. Hippocampi samples were collected for oxidative biochemistry analyses through antioxidant capacity against peroxyl (ACAP), lipid peroxidation (LPO), and nitrite (NO) levels. Also, brain-derived neurotrophic factor (BDNF) gene expression (RT-qPCR) and proteomic profile analyses were performed. The results showed that exposure to both F concentrations during pregnancy and lactation increased the F bioavailability, triggered redox imbalance featured by a decrease of ACAP, increase of LPO and NO levels, BDNF overexpression and changes in the hippocampus proteome. These findings raise novel questions regarding potential repercussions on the hippocampus structure and functioning in the different cognitive domains.
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http://dx.doi.org/10.1016/j.ecoenv.2020.111437DOI Listing
January 2021

Effects of Fluoride Long-Term Exposure over the Cerebellum: Global Proteomic Profile, Oxidative Biochemistry, Cell Density, and Motor Behavior Evaluation.

Int J Mol Sci 2020 Oct 2;21(19). Epub 2020 Oct 2.

Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará, Belém, PA 66075-110, Brazil.

Although the literature does not provide evidence of health risks from exposure to fluoride (F) in therapeutic doses, questions remain about the effects of long-term and high-dose use on the function of the central nervous system. The objective of this study was to investigate the effect of long-term exposure to F at levels similar to those found in areas of artificial water fluoridation and in areas of endemic fluorosis on biochemical, proteomic, cell density, and functional parameters associated with the cerebellum. For this, mice were exposed to water containing 10 mg F/L or 50 mg F/L (as sodium fluoride) for 60 days. After the exposure period, the animals were submitted to motor tests and the cerebellum was evaluated for fluoride levels, antioxidant capacity against peroxyl radicals (ACAP), lipid peroxidation (MDA), and nitrite levels (NO). The proteomic profile and morphological integrity were also evaluated. The results showed that the 10 mg F/L dose was able to decrease the ACAP levels, and the animals exposed to 50 mg F/L presented lower levels of ACAP and higher levels of MDA and NO. The cerebellar proteomic profile in both groups was modulated, highlighting proteins related to the antioxidant system, energy production, and cell death, however no neuronal density change in cerebellum was observed. Functionally, the horizontal exploratory activity of both exposed groups was impaired, while only the 50 mg F/L group showed significant changes in postural stability. No motor coordination and balance impairments were observed in both groups. Our results suggest that fluoride may impair the cerebellar oxidative biochemistry, which is associated with the proteomic modulation and, although no morphological impairment was observed, only the highest concentration of fluoride was able to impair some cerebellar motor functions.
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http://dx.doi.org/10.3390/ijms21197297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582550PMC
October 2020

Long-Term Exposure to Inorganic Mercury Leads to Oxidative Stress in Peripheral Blood of Adult Rats.

Biol Trace Elem Res 2021 Aug 30;199(8):2992-3000. Epub 2020 Sep 30.

Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará, Rua Augusto Corrêa n° 1, Campus do Guamá, Belém, Pará, 66075-110, Brazil.

Mercury chloride (HgCl) is a compound found in the environment that presents low risk due to low liposolubility. Considering the importance of blood as access rout to the systemic distribution of this toxicant to the organism as well as functions performed by it, this study aimed to investigate the effects of HgCl on the peripheral blood of rats, evaluating the oxidative biochemistry, blood count, and morphology of cell populations. For this, 20 adult Wistar male rats were divided into control (n = 10) and exposed (n = 10) groups and received distilled water or HgCl at a dose of 0.375 mg/kg for 45 days, respectively, through intragastric gavage. Then, the animals were euthanized and the blood was collected for total mercury (Hg) levels determination, complete blood and reticulocyte count, oxidative biochemistry by Trolox Equivalent Antioxidant Capacity (TEAC), reduced glutathione (GSH) levels, superoxide dismutase activity (SOD), thiobarbituric acid reactive substances (TBARS), and nitric oxide (NO), in blood cells and plasma. Long-term exposure increased total Hg in plasma and blood cells. In blood cells, only TEAC has decreased; in plasma, the HgCl increased TBARS and NO levels, followed by a decrease in TEAC and GSH levels. There were no quantitative changes in reticulocytes, erythrocytes, and hemoglobin; however, the number of leukocytes have increased and platelets have decreased. Our results suggest that even in the face of low toxicity when compared with other mercury species, HgClat low doses is able to modulate the systemic redox balance and affect some blood cell populations.
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http://dx.doi.org/10.1007/s12011-020-02411-5DOI Listing
August 2021

Chronic methylmercury exposure causes spinal cord impairment: Proteomic modulation and oxidative stress.

Food Chem Toxicol 2020 Dec 25;146:111772. Epub 2020 Sep 25.

Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará, Belém, Brazil. Electronic address:

Methylmercury (MeHg) is considered by the World Health Organization (WHO) as one of the chemicals of greatest public health concern. Although central nervous system (CNS) is the main target organ, the effects over the spinal cord are not well understood, especially in chronic exposure at similar doses to those faced by humans. This study aimed to investigate possible changes on global proteomic profile and oxidative biochemistry status of rats spinal cord, related to the maintenance and balance of the organism functioning, mimicking a human daily exposure by diet (chronic and with relatively low levels). For this, 28 adults male Wistar rats were divided into two groups: MeHg group, which was intoxicated by intragastric gavage with MeHg at a dose of 0.04 mg/kg/day for 60 days, and control group, that received only vehicle. After the exposure period, the spinal cords were collected for evaluation of total mercury levels, proteomic profile, with further bioinformatic overrepresentation analysis (ORA), and oxidative biochemistry, by analyzing the antioxidant capacity against peroxyl radicals (ACAP), lipid peroxidation (LPO), nitrite levels, measurement of Trolox Equivalent Antioxidant Capacity (TEAC) and Reduced Glutathione (GSH). The MeHg exposure increased total mercury levels in spinal cord parenchyma, which increased lipid peroxidation and nitrite levels , and reduced antioxidant status. The proteomic analysis showed several proteins related to biological processes, cellular components and molecular functions. Moreover, according to the ORA analysis, the proteins are involved in processes such as mitochondrial activity, stress response, cytoskeleton and apoptosis. Therefore, we concluded that exposure to low doses of MeHg can activate the oxidative stress pathway and thus, modulate the status of regulation of several important proteins.
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http://dx.doi.org/10.1016/j.fct.2020.111772DOI Listing
December 2020

Hippocampal Impairment Triggered by Long-Term Lead Exposure from Adolescence to Adulthood in Rats: Insights from Molecular to Functional Levels.

Int J Mol Sci 2020 Sep 21;21(18). Epub 2020 Sep 21.

Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará, Belém, PA 66075-110, Brazil.

Lead (Pb) is an environmental and occupational neurotoxicant after long-term exposure. This study aimed to investigate the effects of systemic Pb exposure in rats from adolescence to adulthood, evaluating molecular, morphologic and functional aspects of hippocampus. For this, male Wistar rats were exposed to 50 mg/kg of Pb acetate or distilled water for 55 days by intragastric gavage. For the evaluation of short-term and long-term memories, object recognition and step-down inhibitory avoidance tests were performed. At the end of the behavioral tests, the animals were euthanized and the hippocampus dissected and processed to the evaluation of: Pb content levels in hippocampal parenchyma; Trolox equivalent antioxidant capacity (TEAC), glutathione (GSH) and malondialdehyde (MDA) levels as parameters of oxidative stress and antioxidant status; global proteomic profile and neuronal degeneration by anti-NeuN immunohistochemistry analysis. Our results show the increase of Pb levels in the hippocampus of adult rats exposed from adolescence, increased MDA and GSH levels, modulation of proteins related to neural structure and physiology and reduced density of neurons, hence a poor cognitive performance on short and long-term memories. Then, the long-term exposure to Pb in this period of life may impair several biologic organizational levels of the hippocampal structure associated with functional damages.
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http://dx.doi.org/10.3390/ijms21186937DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554827PMC
September 2020

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

PLoS One 2020 30;15(7):e0236161. Epub 2020 Jul 30.

Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará (UFPA), Belém, Pará, Brazil.

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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0236161PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7392256PMC
September 2020

Evaluation of Cerebellar Function and Integrity of Adult Rats After Long-Term Exposure to Aluminum at Equivalent Urban Region Consumption Concentrations.

Biol Trace Elem Res 2021 Apr 20;199(4):1425-1436. Epub 2020 Jun 20.

Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará, Street Augusto Corrêa N. 1, Campus do Guamá, Belém, PA, 66075-900, Brazil.

High amounts of aluminum (Al) are found in soil and water. It is highly bioavailable, which makes it an important agent of environmental imbalance. Moreover, Al is considered a neurotoxic agent that is associated with several neurodegenerative diseases. Thus, this study investigated the effects of long-term Al chloride (AlCl) exposure on motor behavior, oxidative biochemistry, and cerebellar tissue parameters. For this, adult Wistar rats were divided into three groups: Al-D1 (8.3 mg kg day), Al-D2 (5.2 mg kg day), and control (distilled water); all groups were orally exposed for 60 days by intragastric gavage. After the exposure period, animals performed the open field, elevated plus maze, rotarod, and beam walking tests. Then, the blood and cerebellum were collected to evaluate Al levels and biochemical and morphological analyses, respectively. Our results demonstrate that animals exposed to Al doses presented a higher Al level in the blood. In the spontaneous locomotor activity, Al exposure groups had traveled a lower total distance when compared with the control group. There was no statistically significant difference (p > 0.05) between exposed and control groups when anxiogenic profile, forced locomotion, fine motor coordination/balance, pro-oxidative parameter, and density Purkinje cells were compared. Thus, aluminum exposure in equivalent doses to human consumption in urban regions did not promote significant changes in the cerebellum or motor parameters.
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http://dx.doi.org/10.1007/s12011-020-02244-2DOI Listing
April 2021

Genotoxic effect of non-lethal concentrations of minocycline in human glial cell culture.

Biomed Pharmacother 2020 Aug 30;128:110285. Epub 2020 May 30.

Laboratory of Functional and Structural Biology, Institute of Biological Science, Federal University of Pará, Belém, Brazil. Electronic address:

Minocycline has been proposed as a neuroprotective agent with pleiotropic effects on several experimental models of neurodegenerative diseases, including microglial inhibition. However, although most studies have focused on the central actions of minocycline in affecting microglial functions, other central nervous system (CNS) cell types may also be affected by this drug toxicity. Hence, considering that glial cells play a pivotal role on CNS physiology and are the main responsible for neuronal integrity, a comprehensive investigation on the effects of minocycline treatment on human glial cells is mandatory before translational studies to afford neuroprotection in humans. Therefore, we explored the cytotoxic and genotoxic effects of minocycline at different concentrations in glial cells using an in vitro model. To achieve this, U87 glial cell were exposed to 10-50 μg/mL for 24 h. After exposure, cell viability, general metabolic status and genotoxic assays were performed. No changes were observed in cell viability, however, the general metabolic status decreased over 20 μg/mL. In addition, although no chromossome aberrations were observed, evidences of genotoxicity, such as increase on micronucleus, buds and bridges, were observed from 10 μg/mL. These results suggest that minocycline may induce genotoxic effects even at concentrations considered previously safe and should be used with caution in translational studies.
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http://dx.doi.org/10.1016/j.biopha.2020.110285DOI Listing
August 2020

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

Int J Mol Sci 2020 May 18;21(10). Epub 2020 May 18.

Laboratory of Functional and Structural Biology, Biological Sciences Institute, Federal University of Pará, Belém 66075-110, Brazil.

In traditional communities of the Brazilian Amazon, the copaiba oleoresin ( 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 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.
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http://dx.doi.org/10.3390/ijms21103568DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278981PMC
May 2020

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

Int J Mol Sci 2020 May 18;21(10). Epub 2020 May 18.

Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará, Belém, Pará 66075-110, Brazil.

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.
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http://dx.doi.org/10.3390/ijms21103571DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7279001PMC
May 2020

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

Biol Trace Elem Res 2020 Dec 11;198(2):575-582. Epub 2020 Mar 11.

Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará (UFPA), Belém, PA, Brazil.

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 (AlCl) 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 AlCl 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, AlCl 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.
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http://dx.doi.org/10.1007/s12011-020-02091-1DOI Listing
December 2020

Long-term exposure to lead reduces antioxidant capacity and triggers motor neurons degeneration and demyelination in spinal cord of adult rats.

Ecotoxicol Environ Saf 2020 May 6;194:110358. Epub 2020 Mar 6.

Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará, Belém, State of Pará, Brazil. Electronic address:

Lead is a toxic metal found in environment with great neurotoxic potential. The main effect is associated with impairments in hippocampus and cerebellum, driving to cognitive and motor dysfunctions, however, there is a lack of evidences about the effects over the spinal cord. In this way, we aimed to investigate in vivo the effects of long-term exposure to lead acetate in oxidative biochemistry and morphology of rats' spinal cord. For this, 36 male Wistar rats (Rattus norvegicus) were divided into the group exposed to 50 mg/kg of lead acetate and control group, which received only distilled water, both groups through intragastric gavage, for 55 days. After the exposure period, the animals were euthanized and the spinal cords were collected to perform the analyses of lead levels quantification, oxidative biochemistry evaluation by levels of malondialdehyde (MDA), nitrites and the antioxidant capacity against peroxyl radicals (ACAP). Besides, morphological evaluation with quantitative analysis of mature and motor neurons and reactivity to myelin basic protein (MBP). Our results showed high levels of lead in spinal cord after long-term exposure; there was a reduction on ACAP level; however, there was no difference observed in MDA and nitrite levels. Moreover, there was a reduction of mature and motor neurons in all three regions, and a reduction of immunolabeling of MBP in the thoracic and lumbar segments. Therefore, we conclude that long-term exposure to lead is able of increasing the levels of the metal in spinal cord, affecting the antioxidant capacity and inducing morphological impairments in spinal cord parenchyma. Our results also suggest that the tissue impairments triggered by lead may be resultant from others molecular mechanisms besides the oxidative stress.
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http://dx.doi.org/10.1016/j.ecoenv.2020.110358DOI Listing
May 2020

Spinal cord neurodegeneration after inorganic mercury long-term exposure in adult rats: Ultrastructural, proteomic and biochemical damages associated with reduced neuronal density.

Ecotoxicol Environ Saf 2020 Mar 18;191:110159. Epub 2020 Jan 18.

Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Para, Belém, PA, Brazil. Electronic address:

Mercury chloride (HgCl) is a chemical pollutant widely found in the environment. This form of mercury is able to promote several damages to the Central Nervous System (CNS), however the effects of HgCl on the spinal cord, an important pathway for the communication between the CNS and the periphery, are still poorly understood. The aim of this work was to investigate the effects of HgCl exposure on spinal cord of adult rats. For this, animals were exposed to a dose of 0.375 mg/kg/day, for 45 days. Then, they were euthanized, the spinal cord collected and we investigated the mercury concentrations in medullary parenchyma and the effects on oxidative biochemistry, proteomic profile and tissue structures. Our results showed that exposure to this metal promoted increased levels of Hg in the spinal cord, impaired oxidative biochemistry by triggering oxidative stress, mudulated antioxidant system proteins, energy metabolism and myelin structure; as well as caused disruption in the myelin sheath and reduction in neuronal density. Despite the low dose, we conclude that prolonged exposure to HgCl triggers biochemical changes and modulates the expression of several proteins, resulting in damage to the myelin sheath and reduced neuronal density in the spinal cord.
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http://dx.doi.org/10.1016/j.ecoenv.2019.110159DOI Listing
March 2020

Aerobic Physical Exercise as a Neuroprotector Strategy for Ethanol Binge-Drinking Effects in the Hippocampus and Systemic Redox Status in Rats.

Oxid Med Cell Longev 2019 4;2019:2415243. Epub 2019 Jul 4.

Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará (UFPA), Belém, PA, Brazil.

The heavy and episodic EtOH drinking pattern, equivalent to weekend consumption, characterizes the binge-drinking pattern and promotes a misbalance of encephalic metabolic functions, concurring to neurodegeneration and cerebral dysfunction. And for being a legal drug, it has global public health and social relevance. In this way, we aimed to investigate the effects of physical training, in a treadmill, on the deleterious effects of EtOH on hippocampal functions, related to memory and learning. For this, we used 40 Wistar rats, divided into four groups: Control group, Trained group (trained animals with doses of distilled water), EtOH group (nontrained animals with doses of 3 g/kg/day of EtOH, 20% /), and Trained+EtOH group (trained animals exposed to EtOH). The physical exercise was performed by running on a treadmill for 5 days a week for 4 weeks, and all doses of EtOH were administered through intragastric gavage in four repeated cycles of EtOH in binge. After the experimental period, the animals were submitted to the object recognition task and Morris water maze test, and after being euthanized, the blood and hippocampus were collected for Trolox Equivalent Antioxidant Capacity (TEAC), Reduced Glutathione Content (GSH), and Nitrite and Lipid Peroxidation (LPO) level measurements. Our results showed that EtOH caused marked oxidative stress and mnemonic damage, and the physical exercise promoted neuroprotective effects, among them, the modulation of oxidative biochemistry in plasma (by restoring GSH levels) and in the hippocampus (by reducing LPO levels and increasing antioxidant parameters) and cognitive function improvement. Therefore, physical exercise can be an important prophylactic and therapeutic tool in order to ameliorate and even prevent the deleterious effects of EtOH on cognitive functions.
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http://dx.doi.org/10.1155/2019/2415243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6637690PMC
February 2020

Methylmercury intoxication and cortical ischemia: Pre-clinical study of their comorbidity.

Ecotoxicol Environ Saf 2019 Jun 10;174:557-565. Epub 2019 Mar 10.

Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará, Belém, PA, Brazil. Electronic address:

Stroke is one of the main causes of human disability worldwide. Ischemic stroke is mostly characterized by metabolic collapse and fast tissue damage, followed by secondary damage in adjacent regions not previously affected. Heavy metals intoxication can be associated with stroke incidence, because of their damaging action in the vascular system. Mercury, in particular, possesses a high tropism by metabolically active regions, such as the brain. In the present study we sought to evaluate whether methylmercury (MeHg) intoxication can aggravate the tissue damage caused by an ischemic stroke induced by microinjections of endothelin-1 (ET-1) into the motor cortex of adult rats. Following MeHg intoxication by gavage (0.04 mg/kg/day) during 60 days, the animals were injected with ET-1 (1 μl, 40 pmol/μl) or vehicle (1 μl). After 7 days, all animals were submitted to behavioral tests and then their brains were processed to biochemical and immunohistochemical analyses. We observed that long-term MeHg intoxication promoted a significant Hg deposits in the motor cortex, with concomitant increase of microglial response, followed by reduction of the neuronal population following ischemia and MeHg intoxication, as well as disturbance in the antioxidant defense mechanisms by misbalance of oxidative biochemistry with increase of both lipid peroxidation and nitrite levels, associated to behavioral deficits. MeHg exposure and cortical ischemia demonstrated that both injuries are able of causing significant neurobehavioural impairments in motor coordination and learning accompanied of an exacerbated microglial activation, oxidative stress and neuronal loss in the motor cortex, indicating that MeHg as a source of metabolic disturbance can act as an important increasing factor of ischemic events in the brain.
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http://dx.doi.org/10.1016/j.ecoenv.2019.03.009DOI Listing
June 2019

Neurochemical dysfunction in motor cortex and hippocampus impairs the behavioral performance of rats chronically exposed to inorganic mercury.

J Trace Elem Med Biol 2019 Mar 14;52:143-150. Epub 2018 Dec 14.

Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará, Belém, Pará, Brazil. Electronic address:

Chronic exposure to mercury chloride (HgCl) has been shown to promote oxidative stress and cell death in the central nervous system of adult rats displaying motor and cognitive impairments. However, there are no investigations about neurochemical function after this type of exposure in rodents that may be associated with those behavioral changes already reported. Thus, the aim of this study was to analyze glutamatergic and GABAergic dysfunctions in the motor cortex and hippocampus of adult rats, in a model of chronic exposure to HgCl in. Twenty rats were exposed to a daily dose of 0.375 mg/kg for 45 days. After this period, they were submitted to motor and cognitive functions tests and euthanized to collect the motor cortex and hippocampus for measurement of mercury (Hg) levels in the parenchyma and neurochemical assays for analysis of glutamatergic and GABAergic functions. It was observed that chronic exposure to HgCl promoted increase in total Hg levels in these two brain areas, with changes in glutamatergic transport, but without changes in GABAergic transport. Functionally this model of exposure caused the decrease of the spontaneous motor locomotion and in the process of learning and memory. In this way, our results provide evidences that glutamatergic neurochemical dysfunction can be pointed out as a strong causal factor of motor and cognitive deficits observed in rats exposed to this HgCl.
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http://dx.doi.org/10.1016/j.jtemb.2018.12.008DOI Listing
March 2019

Proteomic approach underlying the hippocampal neurodegeneration caused by low doses of methylmercury after long-term exposure in adult rats.

Metallomics 2019 02;11(2):390-403

Laboratory of Structural and Functional Biology, Institute of Biological Sciences, Federal University of Pará, No 125, Augusto Corrêa Street N. 01, Guamá, 66075-900, Belém, Pará, Brazil.

Methylmercury (MeHg) is an important toxicant that causes cognitive dysfunctions in humans. This study aimed to investigate the proteomic and biochemical alterations of the hippocampus associated with behavioural consequences of low doses of MeHg in a long-term exposure model, and to realistically mimic in vivo the result of human exposure to this toxicant. Adult Wistar male rats were exposed to a dose of MeHg at 0.04 mg kg-1 day-1 by gavage for 60 days. Total mercury (Hg) content was significantly increased in the hippocampal parenchyma. The increase in the Hg levels was capable of reducing neuron and astrocyte cell density in the CA1, CA3, hilus and dentate gyrus regions, increasing both malondialdehyde and nitrite levels and decreasing antioxidant capacity against peroxyl radicals. The proteomic analysis detected 1041 proteins with altered expression due to MeHg exposure, including 364 proteins with no expression, 295 proteins with de novo expression and 382 proteins with up- or down-regulated expression. This proteomic approach revealed alterations in pathways related to chemical synapses, metabolism, amino acid transport, cell energy, neurodegenerative processes and myelin maintenance. Therefore, even at low doses of MeHg exposure, it is possible to cause hippocampal damage in adult rats at many organisational levels, triggering oxidative stress and proteome misbalance, featuring a neurodegenerative process and culminating in long- and short-term memory and learning deficits.
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http://dx.doi.org/10.1039/c8mt00297eDOI Listing
February 2019

Chronic ethanol forced administration from adolescence to adulthood reduces cell density in the rat spinal cord.

Tissue Cell 2018 Dec 24;55:77-82. Epub 2018 Oct 24.

Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará, Augusto Corrêa Street n. 1, Guamá, Belém-Pará, 66075-900, Brazil. Electronic address:

Ethanol (EtOH) consumption is a risk factor for central nervous system damage, especially during adolescence. This study aimed to investigate the possible effects of chronic EtOH forced administration on gray and white matter of the spinal cord, from adolescence to adulthood. For this, male Wistar rats were administered EtOH by gavage (6.5 g/kg/day; 22.5% w/v) from the 35th to the 90th day of life, while control animals received only distilled water. After exposure, animals were euthanized and their spinal cords processed to obtain cervical and thoracic segments for histological analyses. Quantitative analyses of total cell density and motor neurons of white and gray matter from the ventral horns were evaluated. Forced EtOH administration model showed a decrease in the motoneuron density in the spinal cord in both segments evaluated. Analyses of total cell density showed that the cervical segment was more susceptible to damages promoted by EtOH, with a significant decrease in cell density. Our results showed that chronic EtOH exposure during adolescence could promote injuries to the spinal cord, with neurodegeneration of motoneurons and other cell types present in neural parenchyma.
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http://dx.doi.org/10.1016/j.tice.2018.10.001DOI Listing
December 2018

Low doses of methylmercury exposure during adulthood in rats display oxidative stress, neurodegeneration in the motor cortex and lead to impairment of motor skills.

J Trace Elem Med Biol 2019 Jan 11;51:19-27. Epub 2018 Sep 11.

Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará, Belém, PA, Brazil. Electronic address:

Despite the vast distribution among tissues, the central nervous system (CNS) represents the main target of methylmercury (MeHg) toxicity. However, few studies have evaluated the effects of MeHg exposure on the CNS at equivalent doses to human environmental exposure. In our study, we evaluated the motor cortex, an important area of motor control, in adult rats chronically exposed to MeHg in a concentration equivalent to those found in fish-eating populations exposed to mercury (Hg). The parameters evaluated were total Hg accumulation, oxidative stress, tissue damage, and behavioral assessment in functional actions that involved this cortical region. Our results show in exposed animals a significantly greater level of Hg in the motor cortex; increase of nitrite levels and lipid peroxidation, associated with decreased antioxidant capacity against peroxyl radicals; reduction of neuronal and astrocyte density; and poor coordination and motor learning impairment. Our data showed that chronic exposure at low doses to MeHg is capable of promoting damages to the motor cortex of adult animals, with changes in oxidative biochemistry misbalance, neurodegeneration, and motor function impairment.
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http://dx.doi.org/10.1016/j.jtemb.2018.09.004DOI Listing
January 2019
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