Publications by authors named "Marcia Cristina Freitas Silva"

13 Publications

  • Page 1 of 1

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jtemb.2021.126820DOI 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12011-020-02492-2DOI Listing
October 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fct.2020.111772DOI Listing
December 2020

Behavioural, electrocorticographic, and electromyographic alterations induced by Nerium oleander ethanolic extract: Anticonvulsant therapeutics assessment.

Neurotoxicology 2020 05 5;78:21-28. Epub 2020 Feb 5.

Laboratory of Pharmacology and Toxicology of Natural Products, Institute of Biological Sciences, Federal University of Pará, UFPA, Belém, Pará, Brazil.

Nerium oleander Linn. is an Apocynaceae shrub which is among the most toxic ornamental plants. Although seizures are one of the symptoms associated with N. Oleander poisoning in humans, only a few studies are available on the behavioural and electrophysiological alterations caused by this plant poisoning. This study aimed at providing a thorough description of the electroencephalographic (EEG) and electromyographic (EMG) profiles throughout the experimental poisoning of Wistar rats (200-250 g) using ethanolic extract of N. oleander (EENO). Further, seizure control was assessed using different anticonvulsants. Male Wistar rat's behaviour was assessed upon EENO (150 mg/kg) administration and the animals were evaluated for muscle and neural activities through EMG and EEG recordings, respectively. The behavioural test showed two distinct phases of CNS activity: Phase I - myorelaxation and depression, and Phase II - excitability (agitated behaviour and seizures). Such phases were consistent with the EEG and EMG tracing patterns attained. Within the first 400 s of the recordings, during Phase I, the EMG showed no tracing amplitude variation. Later, the tracing pattern was changed and an intensification of the muscle contraction power in higher frequencies was observed during Phase II. The EEG showed initially a slight flattening in the tracings with a reduction in the intensity of the signal as per spectrogram of frequency attained. Thereafter, during Phase II, much higher amplitude tracings could be noted with an intensification of the signal, compatible with seizures. Seizure control was evaluated using four agents: phenytoin, phenobarbital, diazepam and scopolamine (at 10 mg/kg in all cases). While scopolamine was not effective in the seizure control, diazepam was the most efficient drug for the attenuation of the poisoning. Our results indicate the possibility of including phenytoin, phenobarbital and diazepam, mainly the latter, in the poisoning therapeutic protocol, including for those individuals who could be more susceptible to the poisoning by Nerium oleander as in the case of epileptic patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuro.2020.02.001DOI 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ecoenv.2019.110159DOI Listing
March 2020

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c8mt00297eDOI Listing
February 2019

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jtemb.2018.09.004DOI Listing
January 2019

Repeated Cycles of Binge-Like Ethanol Intake in Adolescent Female Rats Induce Motor Function Impairment and Oxidative Damage in Motor Cortex and Liver, but Not in Blood.

Oxid Med Cell Longev 2018 19;2018:3467531. Epub 2018 Sep 19.

Laboratory of Pharmacology of Inflammation and Behavior, Faculty of Pharmacy, Institute of Health Science, Federal University of Pará, Belém, PA, Brazil.

Moderate ethanol consumption (MEC) is increasing among women. Alcohol exposure usually starts in adolescence and tends to continue until adulthood. We aimed to investigate MEC impacts during adolescence until young adulthood of female rats. Adolescent female Wistar rats received distilled water or ethanol (3 g/kg/day), in a 3 days on-4 days off paradigm (binge drinking) for 1 and 4 consecutive weeks. We evaluate liver and brain oxidative damage, peripheral oxidative parameters by SOD, catalase, thiol contents, and MDA, and behavioral motor function by open-field, pole, beam-walking, and rotarod tests. Our results revealed that repeated episodes of binge drinking during adolescence displayed lipid peroxidation in the liver and brain. Surprisingly, such oxidative damage was not detectable on blood. Besides, harmful histological effects were observed in the liver, associated to steatosis and loss of parenchymal architecture. In addition, ethanol intake elicited motor incoordination, bradykinesia, and reduced spontaneous exploratory behavior in female rats.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2018/3467531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6169231PMC
December 2018

Hippocampal Dysfunction Provoked by Mercury Chloride Exposure: Evaluation of Cognitive Impairment, Oxidative Stress, Tissue Injury and Nature of Cell Death.

Oxid Med Cell Longev 2018 10;2018:7878050. Epub 2018 Apr 10.

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

Mercury (Hg) is a highly toxic metal, which can be found in its inorganic form in the environment. This form presents lower liposolubility and lower absorption in the body. In order to elucidate the possible toxicity of inorganic Hg in the hippocampus, we investigated the potential of low doses of mercury chloride (HgCl) to promote hippocampal dysfunction by employing a chronic exposure model. For this, 56 rats were exposed to HgCl (0.375 mg/kg/day) via the oral route for 45 days. After the exposure period, the animals were submitted to the cognitive test of fear memory. The hippocampus was collected for the measurement of total Hg levels, analysis of oxidative stress, and evaluation of cytotoxicity, apoptosis, and tissue injury. It was observed that chronic exposure to inorganic Hg promotes an increase in mercury levels in this region and damage to short- and long-term memory. Furthermore, we found that this exposure model provoked oxidative stress, which led to cytotoxicity and cell death by apoptosis, affecting astrocytes and neurons in the hippocampus. Our study demonstrated that inorganic Hg, even with its low liposolubility, is able to produce deleterious effects in the central nervous system, resulting in cognitive impairment and hippocampal damage when administered for a long time at low doses in rats.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2018/7878050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5914100PMC
October 2018

Methylmercury Intoxication Promotes Metallothionein Response and Cell Damage in Salivary Glands of Rats.

Biol Trace Elem Res 2018 Sep 14;185(1):135-142. Epub 2018 Jan 14.

Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Para, Street Augusto Correa N. 01, Guamá, Belém, Para, 66075-900, Brazil.

Environmental and occupational mercury exposure is considered a major public health issue. Despite being well known that MeHg exposure causes adverse effects in several physiologic functions, MeHg effects on salivary glands still not completely elucidated. Here, we investigated the cellular MeHg-induced damage in the three major salivary glands (parotid, submandibular, and sublingual) of adult rats after chronic, systemic and low doses of MeHg exposure. Rats were exposed by 0.04 mg/kg/day over 60 days. After that, animals were euthanized and all three glands were collected. We evaluated total Hg accumulation, metallothionein I/II (MT I/II), α-smooth muscle actin (α-SMA), and cytokeratin 18 (CK18) immune expression. Our results have showed that MeHg is able to disrupt gland tissue and to induce a protective mechanism by MT I/II expression. We also showed that cell MT production is not enough to protect gland tissue against cellular structural damage seen by reducing marking of cytoskeletal proteins as CK18 and α-SMA. Our data suggest that chronic MeHg exposure in low-daily doses is able to induce cellular damage in rat salivary glands.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12011-017-1230-9DOI Listing
September 2018

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

Metallomics 2017 12 30;9(12):1778-1785. Epub 2017 Oct 30.

Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará, Street Augusto Corrêa N. 01, Guamá, Belém, Pará 66075-900, Brazil.

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

Download full-text PDF

Source
http://dx.doi.org/10.1039/c7mt00168aDOI Listing
December 2017

Oxidative Biochemistry Disbalance and Changes on Proteomic Profile in Salivary Glands of Rats Induced by Chronic Exposure to Methylmercury.

Oxid Med Cell Longev 2017 24;2017:5653291. Epub 2017 Jul 24.

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

Methylmercury (MeHg) is one of the most toxic mercury species, which can cause many systemic damages, but little is known about its effect in the salivary glands. This study aimed to analyze the mercury levels, oxidative stress, and proteomic profile in parotid, submandibular, and sublingual salivary glands of rats, after chronic MeHg intoxication. Two groups of twenty male Wistar rats (90 days of age) were used on the experiment. MeHg group was intoxicated by intragastric gavage with MeHg at a dose of 0.04 mg/kg/day for 60 days, while the control group received only oil. After the period of intoxication, the glands were collected for evaluation of total mercury levels, proteomic profile, and oxidative balance by analyzing the antioxidant capacity against peroxyl radicals (ACAP), lipid peroxidation (LPO), and nitrite levels. Our results have showed that mercury levels were significant in all three glands compared to the respective control. It also showed lower levels of ACAP, as well as higher LPO and nitrite levels. The proteomic profile presented impairments on structural components of cytoskeleton, metabolic pathways, and oxidative biochemistry. Thus, the exposure to MeHg was able to generate oxidative stress that could be associated with changes in the proteomic profile of salivary glands.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2017/5653291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5546058PMC
April 2018
-->