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

Federal University of Pará. Institute of Biological Sciences. Laboratory of Functional and Structural Biology. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Functional and Structural Biology. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Functional and Structural Biology. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Functional and Structural Biology. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Functional and Structural Biology. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Molecular Pharmacology. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Functional and Structural Biology. Belém, PA, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de Cultura de Tecidos e Citogenética. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de Cultura de Tecidos e Citogenética. Ananindeua, PA, Brasil / Federal University of Pará. Institute of Natural Sciences. College of Natural Sciences. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Molecular Pharmacology. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Functional and Structural Biology. Belém, PA, 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

Towards Therapeutic Alternatives for Mercury Neurotoxicity in the Amazon: Unraveling the Pre-Clinical Effects of the Superfruit Açaí (Euterpe oleracea, Mart.) as Juice for Human Consumption

Methylmercury (MeHg) exposure is a serious problem of public health, especially in the Amazon. Exposure in riverine populations is responsible for neurobehavioral abnormalities. It was hypothesized that consumption of Amazonian fruits could protect by reducing mercury accumulation. This work analyzed the effects of commercial samples of Euterpe oleracea (EO) for human consumption (10 μL/g) against MeHg i.p. exposure (2.5 mg/Kg), using neurobehavioral (open field, rotarod and pole tests), biochemical (lipid peroxidation and nitrite levels), aging-related (telomerase reverse transcriptase (TERT) mRNA expression) and toxicokinetic (MeHg content) parameters in mice. Both the pole and rotarod tests were the most sensitive tests accompanied by increased lipid peroxidation and nitrite levels in brains. MeHg reduced TERT mRNA about 50% demonstrating a strong pro-aging effect. The EO intake, similar to that of human populations, prevented all alterations, without changing the mercury content, but avoiding neurotoxicity and premature aging of the Central Nervous System (CNS). Contrary to the hypothesis found in the literature on the possible chelating properties of Amazonian fruits consumption, the effect of EO would be essentially pharmacodynamics, and possible mechanisms are discussed. Our data already support the regular consumption of EO as an excellent option for exposed Amazonian populations to have additional protection against MeHg intoxication

“Special K” Drug on Adolescent Rats: Oxidative Damage and Neurobehavioral Impairments

Ketamine is used in clinical practice as an anesthetic that pharmacologically modulates neurotransmission in postsynaptic receptors, such as NMDA receptors. However, widespread recreational use of ketamine in “party drug” worldwide since the 1990s quickly spread to the Asian orient region. Thus, this study aimed at investigating the behavioral and oxidative effects after immediate withdrawal of intermittent administration of ketamine in adolescent female rats. For this, twenty female Wistar rats were randomly divided into two groups: control and ketamine group (n=10/group). Animals received ketamine (10 mg/kg/day) or saline intraperitoneally for three consecutive days. Three hours after the last administration, animals were submitted to open field, elevated plus-maze, forced swim tests, and inhibitory avoidance paradigm. Twenty-four hours after behavioral tests, the blood and hippocampus were collected for the biochemical analyses. Superoxide dismutase, catalase, nitrite, and lipid peroxidation (LPO) were measured in the blood samples. Nitrite and LPO were measured in the hippocampus. The present findings demonstrate that the early hours of ketamine withdrawal induced oxidative biochemistry unbalance in the blood samples, with elevated levels of nitrite and LPO. In addition, we showed for the first time that ketamine withdrawal induced depressive- and anxiety-like profile, as well as short-term memory impairment in adolescent rodents. The neurobehavioral deficits were accompanied by the hippocampal nitrite and LPO-elevated levels

Towards therapeutic alternatives for mercury neurotoxicity in the amazon: unraveling the pre-clinical effects of the superfruit açaí (euterpe oleracea, mart.) as juice for human consumption

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, grant numbers 27724/2018-2 and 307564/2017-7), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, grant numbers 88887.200500/2018-00 and 88881.172137/2018-01), and Pró-reitoria de Pesquisa da Universidade Federal do Pará (PROPESP—UFPA, s/n)Federal University of Pará. Laboratory of Molecular Pharmacology. Belém, PA, Brazil.Federal University of Pará. Laboratory of Molecular Pharmacology. Belém, PA, Brazil / Federal University of Santa Catarina. Center of Biological Sciences. Laboratory of Neurochemical Investigation. Florianópolis, SC, Brazil.Federal University of Pará. Laboratory of Molecular and Cellular Neurochemistry. Belém, PA, Brazil.Federal University of Pará. Laboratory of Molecular Pharmacology. Belém, PA, Brazil.Federal University of Pará. Laboratory of Molecular Pharmacology. Belém, PA, Brazil.Federal University of Pará. Laboratory of Molecular Pharmacology. Belém, PA, Brazil.Federal University of Pará. Laboratory of Molecular Pharmacology. Belém, PA, Brazil.Federal University of Pará. Laboratory of Molecular Pharmacology. Belém, PA, Brazil.Federal University of Pará. Laboratory of Molecular Pharmacology. Belém, PA, Brazil / University of Oxford. Department of Pharmacology. Laboratory of Experimental Neuropathology. Oxford, OX. UK.Federal University of Pará. Laboratory of Pharmacology of Inflammation and Behavior. Belém, PA, Brazil.Federal University of Pará. Laboratory of Pharmacology of Inflammation and Behavior. Belém, PA, Brazil.Federal University of Pará. Centre for Valorisation of Amazonian Bioactive Compounds. Belém, PA, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ophir Loyola Hospital. Laboratory of Molecular Biology. Belém, PA, Brazil.Federal University of Pará. Laboratory of Functional and Structural Biology. Belém, PA, Brazil.Federal University of Pará. Laboratory of Molecular and Cellular Neurochemistry. Belém, PA, BrazilFederal University of Pará. Laboratory of Molecular Pharmacology. Belém, PA, Brazil / University of Oxford. Department of Pharmacology. Laboratory of Experimental Neuropathology. Oxford, UK.Methylmercury (MeHg) exposure is a serious problem of public health, especially in the Amazon. Exposure in riverine populations is responsible for neurobehavioral abnormalities. It was hypothesized that consumption of Amazonian fruits could protect by reducing mercury accumulation. This work analyzed the effects of commercial samples of Euterpe oleracea (EO) for human consumption (10 μL/g) against MeHg i.p. exposure (2.5 mg/Kg), using neurobehavioral (open field, rotarod and pole tests), biochemical (lipid peroxidation and nitrite levels), aging-related (telomerase reverse transcriptase (TERT) mRNA expression) and toxicokinetic (MeHg content) parameters in mice. Both the pole and rotarod tests were the most sensitive tests accompanied by increased lipid peroxidation and nitrite levels in brains. MeHg reduced TERT mRNA about 50% demonstrating a strong pro-aging effect. The EO intake, similar to that of human populations, prevented all alterations, without changing the mercury content, but avoiding neurotoxicity and premature aging of the Central Nervous System (CNS). Contrary to the hypothesis found in the literature on the possible chelating properties of Amazonian fruits consumption, the effect of EO would be essentially pharmacodynamics, and possible mechanisms are discussed. Our data already support the regular consumption of EO as an excellent option for exposed Amazonian populations to have additional protection against MeHg intoxicatio

Binge Drinking of Ethanol during Adolescence Induces Oxidative Damage and Morphological Changes in Salivary Glands of Female Rats

This study investigates morphological and biochemistry effects of binge ethanol consumption in parotid (PG) and submandibular (SG) salivary glands of rats from adolescence to adulthood. Female Wistar rats (n=26) received ethanol at 3 g/kg/day (20% w/v) for 3 consecutive days/week from the 35th until the 62nd day of life. Animals were treated in two periods: 1 week (G1) and 4 weeks (G2), with a control (treated with distilled water) and an ethanol group to each period. In morphological analysis, morphometric and immunohistochemistry evaluation for smooth muscle actin (αSMA), cytokeratin-18 (CK-18), and vimentin (VIM) were made. Biochemical changes were analyzed by concentration of nitrites and levels of malondialdehyde (MDA). The difference between groups in each analysis was evaluated by Mann-Whitney U test or Student’s t-test (p≤0.05). PG showed, at one week of ethanol exposure, lower CK-18 and α-SMA expression, as well as MDA levels. After four weeks, lower CK-18 and higher MDA levels were observed in PG exposed to ethanol, in comparison to control group. SG showed lower α-SMA expression after 1 and 4 weeks of ethanol exposure as well as higher MDA levels after 1 week. Ethanol binge consumption during adolescence promotes tissue and biochemical changes with only one-week binge in acinar and myoepithelial PG cells

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

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