Methylmercury Promotes Oxidative Stress and Activation of Matrix Metalloproteinases: Cardiovascular Implications

Preclinical and clinical studies worldwide have shown an association between methylmercury (MeHg) poisoning and the risk of developing cardiovascular diseases such as arrhythmias, arterial hypertension, atherosclerosis and myocardial infarction. One of the hypotheses raised for MeHg-induced toxicity is associated with redox imbalance, which promotes oxidative stress by increasing reactive oxygen species (ROS) and reducing the activity of antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx). In addition, oxidative stress and organomercurial compounds are capable of activating MMPs. MMP-2 and MMP-9 participate in pathophysiological processes associated with cardiovascular remodeling. A positive correlation between mercury exposure and increased plasma activity of MMP-2 and circulating MMP-9 has been demonstrated, suggesting a possible mechanism that could increase susceptibility to cardiovascular diseases

Análise do cultivo experimental de ubaia (Eugenia patrisii Vahl. - Myrtaceae): uma frutífera nativa da Amazônia

A ubaia (Eugenia patrisii Vahl.) é uma frutífera nativa da Amazônia cujos frutos são consumidos in natura e na forma de suco. Atualmente a produção desta espécie ainda está restrita ao extrativismo, existindo poucas informações sobre o cultivo e manejo. Neste sentido esta pesquisa avaliou o crescimento vegetativo e a produtividade de frutos de E. patrisii em uma área de cultivo em diferentes condições de adubação. O experimento foi conduzido na Área de Pesquisa Experimental do Instituto Federal de Ciências e Tecnologia do Pará, município de Marabá, Pará, Brasil. As mudas foram produzidas a partir de sementes e cultivadas em condição de sequeiro. Utilizou-se o delineamento em blocos casualizado com três tratamentos: (Argissolo Vermelho-Amarelo + N, P, K); (Argissolo Vermelho-Amarelo + Esterco bovino); (Argissolo Vermelho-Amarelo). A unidade experimental foi composta por 6 plantas, com dez repetições em cinco blocos. Foram avaliados padrões de desenvolvimento vegetal: altura total; diâmetro do colmo; massa seca da parte aérea; massa seca do sistema radicular; massa seca total; relação entre a altura da parte aérea e o diâmetro do colo; relação entre a massa seca da parte aérea e a massa seca do sistema radicular, e Índice de Qualidade de Dickson. Também foram avaliados os parâmetros de produção de frutos: número de frutos; massa média dos frutos e produção de frutos e fenologia. As mudas de ubaia apresentaram desenvolvimento e produção de frutos em todas as condições experimentais com destaque para as cultivadas em tratamento orgânico (Argissolo Vermelho-Amarelo + Esterco Bovino) que apresentaram melhor desenvolvimento e produtividade

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

The importance of fluoride (F) for oral health is well established in the literature. However, evidence suggests that excessive exposure to this mineral is associated with adverse effects at different life stages and may affect many biological systems, especially mineralized tissues. The purpose of this study was to investigate the effects of F exposure during pregnancy and breastfeeding on the alveolar bone of the offspring since the alveolar bone is one of the supporting components of the dental elements. For this, the progeny rats were divided into three groups: control, 10 mg F/L, and 50 mg F/L for 42 (gestational and lactation periods). Analysis of the quantification of F levels in the alveolar bone by particle-induced gamma emission; Raman spectroscopy to investigate the physicochemical aspects and mineral components; computed microtomography to evaluate the alveolar bone microstructure and analyses were performed to evaluate osteocyte density and collagen quantification using polarized light microscopy. The results showed an increase in F levels in the alveolar bone, promoted changes in the chemical components in the bone of the 50 mg F/L animals (p < 0.001), and had repercussions on the microstructure of the alveolar bone, evidenced in the 10 mg F/L and 50 mg F/L groups (p < 0.001). Furthermore, F was able to modulate the content of organic bone matrix, mainly collagen; thus, this damage possibly reduced the amount of bone tissue and consequently increased the root exposure area of the exposed groups in comparison to a control group (p < 0.001). Our findings reveal that Fcan modulate the physicochemical and microstructural dimensions and reduction of alveolar bone height, increasing the exposed root region of the offspring during the prenatal and postnatal period. These findings suggest that F can modulate alveolar bone mechanical strength and force dissipation functionality.This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) – Finance Code 001. R.R.L is a researcher from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and received grant under number 312275/2021-8. Also this research was funded by PROCAD Amazônia – CAPES (23038.005350/2018–78).Peer reviewe

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure &lt; 100 mmHg (n = 1127), estimated glomerular filtration rate &lt; 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Matrix Metalloproteinase 2 as a Pharmacological Target in Heart Failure

Heart failure (HF) is an acute or chronic clinical syndrome that results in a decrease in cardiac output and an increase in intracardiac pressure at rest or upon exertion. The pathophysiology of HF is heterogeneous and results from an initial harmful event in the heart that promotes neurohormonal changes such as autonomic dysfunction and activation of the renin-angiotensin-aldosterone system, endothelial dysfunction, and inflammation. Cardiac remodeling occurs, which is associated with degradation and disorganized synthesis of extracellular matrix (ECM) components that are controlled by ECM metalloproteinases (MMPs). MMP-2 is part of this group of proteases, which are classified as gelatinases and are constituents of the heart. MMP-2 is considered a biomarker of patients with HF with reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF). The role of MMP-2 in the development of cardiac injury and dysfunction has clearly been demonstrated in animal models of cardiac ischemia, transgenic models that overexpress MMP-2, and knockout models for this protease. New research to minimize cardiac structural and functional alterations using non-selective and selective inhibitors for MMP-2 demonstrates that this protease could be used as a possible pharmacological target in the treatment of HF

Studies on the Phytochemical Profile of Ocimum basilicum var. minimum (L.) Alef. Essential Oil, Its Larvicidal Activity and In Silico Interaction with Acetylcholinesterase against Aedes aegypti (Diptera: Culicidae)

Aedes aegypti L. (Diptera: Culicidae) is an important transmitter of diseases in tropical countries and controlling the larvae of this mosquito helps to reduce cases of diseases such as dengue, zika and chikungunya. Thus, the present study aimed to evaluate the larvicidal potential of the essential oil (EO) of Ocimum basilicum var. minimum (L.) Alef. The EO was extracted by stem distillation and the chemical composition was characterized by gas chromatography coupled with mass spectrometry (GC/MS and GC-FID). The larvicidal activity of EO was evaluated against third instar Ae. aegypti following World Health Organization (WHO) standard protocol and the interaction of the major compounds with the acetylcholinesterase (AChE) was evaluated by molecular docking. The predominant class was oxygenated monoterpenes with a concentration of 81.69% and the major compounds were limonene (9.5%), 1,8-cineole (14.23%), linalool (24.51%) and methyl chavicol (37.41%). The O. basilicum var. minimum EO showed unprecedented activity against third instar Ae. aegypti larvae at a dose-dependent relationship with LC50 of 69.91 (&micro;g/mL) and LC90 of 200.62 (&micro;g/mL), and the major compounds were able to interact with AChE in the Molecular Docking assay, indicating an ecological alternative for mosquito larvae control

Potential Biotechnological Applications of Venoms from the <i>Viperidae</i> Family in Central America for Thrombosis

Central America is home to one of the most abundant herpetofauna in the Americas, occupying only 7% of the continent’s total area. Vipers and lizards are among the most relevant venomous animals in medical practice due to the consequences of envenomation from the bite of these animals. A great diversity of biomolecules with immense therapeutic and biotechnological value is contained in their venom. This paper describes the prominent leading representatives of the family Viperidae, emphasizing their morphology, distribution, habitat, feeding, and venom composition, as well as the biotechnological application of some isolated components from the venom of the animals from these families, focusing on molecules with potential anti-thrombotic action. We present the leading protein families that interfere with blood clotting, platelet activity, or the endothelium pro-thrombotic profile. In conclusion, Central America is an endemic region of venomous animals that can provide many molecules for biotechnological applications

“K-Powder” Exposure during Adolescence Elicits Psychiatric Disturbances Associated with Oxidative Stress in Female Rats

Ketamine, also called ‘K-powder’ by abusers, an analog of phencyclidine, primarily acts as an antagonist of N-methyl-D-aspartic acid (NMDA) receptors, therapeutically used as an anesthetic agent. Ketamine also stimulates the limbic system, inducing hallucinations and dissociative effects. At sub-anesthetic doses, ketamine also displays hallucinatory and dissociative properties, but not loss of consciousness. These behavioral consequences have elicited its recreational use worldwide, mainly at rave parties. Ketamine is generally a drug of choice among teenagers and young adults; however, the harmful consequences of its recreational use on adolescent central nervous systems are poorly explored. Thus, the aim of the present study was to characterize the behavioral and biochemical consequences induced by one binge-like cycle of ketamine during the early withdrawal period in adolescent female rats. Adolescent female Wistar rats (n = 20) received intraperitoneally administered ketamine (10 mg/kg/day) for 3 consecutive days. Twenty-four hours after the last administration of ketamine, animals were submitted to behavioral tests in an open field, elevated plus-maze, and forced swimming test. Then, animals were intranasally anesthetized with 2% isoflurane and euthanized to collect prefrontal cortex and hippocampus to assess lipid peroxidation, antioxidant capacity against peroxyl radicals, reactive oxygen species, reduced glutathione, and brain-derived neurotrophic factor (BDNF) levels. Our results found that 24 h after recreational ketamine use, emotional behavior disabilities, such as anxiety- and depression-like profiles, were detected. In addition, spontaneous ambulation was reduced. These negative behavioral phenotypes were associated with evidence of oxidative stress on the prefrontal cortex and hippocampus

One binge-type cycle of alcohol plus ketamine exposure induces emotional-like disorders associated with oxidative damage in adolescent female rats

This work is supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES-FINANCE CODE 001); Conselho Nacional de Desenvolvimento Científico e Tecnológico – CNPq/ Brazil for her Research Productivity Grant (number 311335/2019–5 to CSFM); R.R.L. is a researcher from the CNPq, under grant number 312275/ 2021–8. Research Pro-Rectory of the Federal University of Pará (PROPESP, UFPA, Brazil).Federal University of Pará. Institute of Health Science. Faculty of Pharmacy. Laboratory of Pharmacology of Inflammation and Behavior. Belém, PA, Brazil.Federal University of Pará. Institute of Health Science. Faculty of Pharmacy. Laboratory of Pharmacology of Inflammation and Behavior. Belém, PA, Brazil.Federal University of Pará. Institute of Health Science. Faculty of Pharmacy. Laboratory of Pharmacology of Inflammation and Behavior. Belém, PA, Brazil.Federal University of Pará. Institute of Health Science. Faculty of Pharmacy. Laboratory of Pharmacology of Inflammation and Behavior. Belém, PA, Brazil.Federal University of Pará. Institute of Health Science. Faculty of Pharmacy. Laboratory of Pharmacology of Inflammation and Behavior. Belém, PA, Brazil.University of Pará State. Center for Biological and Health Sciences. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Science. Laboratory of Pharmacology and Toxicology of Cardiovascular System. 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.Ministério da Saúde. Secretaria de Vigilância em Saúde e Ambiente. Instituto Evandro Chagas. Laboratório de Citogenômica e Mutagênese Ambiental. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde e Ambiente. Instituto Evandro Chagas. Laboratório de Citogenômica e Mutagênese Ambiental. Ananindeua, PA, Brasil.Ophir Loyola Hospital. Laboratory of Molecular Biology. Belém, PA, Brazil.Ophir Loyola Hospital. Laboratory of Molecular Biology. Belém, PA, Brazil.Federal University of Pará. Institute of Health Science. Faculty of Pharmacy. Laboratory of Pharmacology of Inflammation and Behavior. Belém, PA, Brazil.Federal University of Pará. Institute of Health Science. Faculty of Pharmacy. Laboratory of Pharmacology of Inflammation and Behavior. Belém, PA, Brazil.Drug abuse is a global public health problem among adolescents, with alcohol often used in association with other psychotropic drugs, such as ketamine. Considering the scarcity of evidence, this study aimed to investigate emotional behavioral effects induced by ethanol plus ketamine co-abuse, as well as oxidative biochemistry, and neurotrophic mediator in the prefrontal cortex and hippocampus in the early withdrawal of adolescent female rats. Animals were divided into control, ethanol, ketamine, and ethanol plus ketamine groups. The protocol administration was performed for 3 consecutive days (binge-like pattern). Behavioral assays of open field, elevated plus maze, and forced swim test were performed. After that, the prefrontal cortex and hippocampus were collected to evaluate oxidative biochemistry (reactive oxygen species-ROS; Antioxidant capacity against peroxyl radicals-ACAP; and lipid peroxidation). We found that isolated or combined ethanol and ketamine exposure displayed anxiety- and depressive-like profile, in a non-synergistically manner during early withdrawal. However, oxidative damage was aggravated in the co-administered animals than in isolated exposed subjects. We concluded that ethanol plus ketamine co-abuse may intensify oxidative damage in the hippocampus and prefrontal cortex in the early withdrawal of adolescent female rats, which was not reflected in the emotional behavioral phenotype

One binge-type cycle of alcohol plus ketamine exposure induces emotional-like disorders associated with oxidative damage in adolescent female rats

Drug abuse is a global public health problem among adolescents, with alcohol often used in association with other psychotropic drugs, such as ketamine. Considering the scarcity of evidence, this study aimed to investigate emotional behavioral effects induced by ethanol plus ketamine co-abuse, as well as oxidative biochemistry, and neurotrophic mediator in the prefrontal cortex and hippocampus in the early withdrawal of adolescent female rats. Animals were divided into control, ethanol, ketamine, and ethanol plus ketamine groups. The protocol administration was performed for 3 consecutive days (binge-like pattern). Behavioral assays of open field, elevated plus maze, and forced swim test were performed. After that, the prefrontal cortex and hippocampus were collected to evaluate oxidative biochemistry (reactive oxygen species-ROS; Antioxidant capacity against peroxyl radicals-ACAP; and lipid peroxidation). We found that isolated or combined ethanol and ketamine exposure displayed anxiety- and depressive-like profile, in a non-synergistically manner during early withdrawal. However, oxidative damage was aggravated in the co-administered animals than in isolated exposed subjects. We concluded that ethanol plus ketamine co-abuse may intensify oxidative damage in the hippocampus and prefrontal cortex in the early withdrawal of adolescent female rats, which was not reflected in the emotional behavioral phenotype. Data availability statement: The datasets used and/or analyzed during the current investigation are available upon reasonable request from the corresponding author