ABSTRACT
Environmental contamination by pharmaceuticals from industrial waste and anthropogenic activities poses adverse health effects on non-target organisms. We evaluated the neurobehavioral and biochemical responses accompanying exposure to ecological relevant concentrations of atenolol (0, 0.1, 1.0, and 10 µg/L) for seven uninterrupted days in adult zebrafish (Danio rerio). Atenolol-exposed fish exhibited anxiety-like behavior, characterized by significant bottom-dwelling with marked reduction in vertical exploration. Atenolol-exposed fish exhibited marked increase in the duration and frequency of aggressive events without altering their preference for conspecifics. Biochemical data using brain samples indicated that atenolol disrupted antioxidant enzyme activities and induced oxidative stress. Exposure to atenolol markedly decreased ATP and AMP hydrolysis without affecting ADP hydrolysis and acetylcholinesterase (AChE) activity. Atenolol significantly upregulated tryptophan hydroxylase 1 (tph1) mRNA expression but downregulated brain-derived neurotrophic factor (bdnf) mRNA. Collectively, waterborne atenolol elicits aggressive and anxiety-like responses in adult zebrafish, accompanied by oxidative stress, reduced nucleotide hydrolysis, altered tph1 and bdnf mRNA expression, which may impact the survival and health of fish in aquatic environment.
Subject(s)
Atenolol , Behavior, Animal , Oxidative Stress , Water Pollutants, Chemical , Zebrafish , Animals , Atenolol/pharmacology , Water Pollutants, Chemical/toxicity , Oxidative Stress/drug effects , Behavior, Animal/drug effects , Tryptophan Hydroxylase/metabolism , Tryptophan Hydroxylase/genetics , Brain-Derived Neurotrophic Factor/metabolismABSTRACT
Recently, social isolation measures were crucial to prevent the spread of the coronavirus pandemic. However, the lack of social interactions affected the population mental health and may have long-term consequences on behavior and brain functions. Here, we evaluated the behavioral, physiological, and molecular effects of a social isolation (SI) in adult zebrafish, and whether the animals recover such changes after their reintroduction to the social environment. Fish were submitted to 12 days of SI, and then reintroduced to social context (SR). Behavioral analyses to evaluate locomotion, anxiety-like and social-related behaviors were performed after SI protocol, and 3 and 6 days after SR. Cortisol and transcript levels from genes involved in neuronal homeostasis (c-fos, egr, bdnf), and serotonergic (5-HT) and dopaminergic (DA) neurotransmission (thp, th) were also measured. SI altered social behaviors in zebrafish such as aggression, social preference, and shoaling. Fish submitted to SI also presented changes in the transcript levels of genes related to neural activity, and 5-HT/DA signaling. Interestingly, most of the behavioral and molecular changes induced by SI were not found again 6 days after SR. Thus, we highlight that SR of zebrafish to their conspecifics played a positive role in social behaviors and in the expression of genes involved in different neuronal signaling pathways that were altered after 12 days of SI. This study brings unprecedented data on the effects of SR in the recovery from SI neurobehavioral alterations, and reinforces the role of zebrafish as a translational model for understanding the neurobiological mechanisms adjacent to SI and resocialization.
Subject(s)
Behavior, Animal , Social Behavior , Social Isolation , Zebrafish , Animals , Social Isolation/psychology , Behavior, Animal/physiology , Hydrocortisone/metabolism , Male , Neurons/metabolism , AnxietyABSTRACT
BACKGROUND: Low back pain (LBP) is the leading cause of disability worldwide, and the burden of LBP is expected to increase in coming decades, particularly in middle-income countries. There is a lack of large and high-quality studies investigating the prevalence of LBP in Brazil. OBJECTIVE: To estimate the point, one-year, and lifetime prevalence of non-specific LBP in adults from the city of São Paulo, Brazil. METHODS: This community-based, cross-sectional study recruited 3000 participants in flow point locations randomly selected from census sectors of São Paulo. Interviews and self-administered questionnaires were used to estimate point prevalence, one-year prevalence, and lifetime prevalence of LBP. RESULTS: The estimate of point prevalence was 9.8% (95% CI: 8.8, 11.0), one-year prevalence was 48.1% (95% CI: 46.3, 49.9), and lifetime prevalence was 62.6% (95% CI: 60.8, 64.3). One-year and lifetime prevalence were higher in females, obese people, people insufficiently active and sedentary, current smokers, people who are exposed to repetitive movements, crouched or kneeling position, people dissatisfied with their job, people a little bit or very stressed, a little bit or very anxious, and a little bit depressed, and people with good and fair or poor general health. Lifetime prevalence was also higher in people exposed to standing positions and exposure to carrying weight. CONCLUSIONS: The high point, one-year, and lifetime prevalence of LBP in Brazil indicates that there is a need for coordinated efforts from government, the private sector, universities, health workers, and civil society to deliver appropriate management of LBP in middle-income countries.
Subject(s)
Low Back Pain , Adult , Brazil/epidemiology , Cross-Sectional Studies , Female , Humans , Low Back Pain/epidemiology , Prevalence , Risk Factors , Surveys and QuestionnairesABSTRACT
The organic selenium compound diphenyl diselenide (DD) has been recognized as an antioxidant and neuroprotective agent, exerting an anti-hyperglycemic effect in experimental models of diabetes. However, the precise mechanisms involved in the protection are unclear. Using the zebrafish (Danio rerio) as a model organism, here we investigated biomarkers underlying the protective effects of DD against hyperglycemia, targeting in a transcriptional approach the redox and insulin-signaling pathway. Fish were fed on a diet containing DD (3â¯mg/kg) for 74 days. In the last 14 days, they were exposed to a 111â¯mM glucose solution to induce a hyperglycemic state. DD reduced blood glucose levels as well as normalized the brain mRNA transcription of four insulin receptors-coding genes (Insra1, Insra2, Insrb1, Insrb2), which were down-regulated by glucose. DD alone caused an up-regulation of relative mRNA transcription in both Insra receptors and glucose transporter 3 genes. DD counteracted hyperglycemia-induced lipid peroxidation, protein and thiol depletion. Along with the decreased activity of antioxidant enzymes SOD and GPx, the brain of hyperglycemic fish presented a reduction in mRNA transcription of FoxO3A, FoxO3B, Nrf2, GPx3A, SOD1, and SOD2 genes. Besides normalizing the transcriptional levels, DD caused an up-regulation of relative mRNAs that encode Nrf2, FoxO1A, FOXO3A, GPx4A, PTP1B, AKT and SelP. Collectively, our findings suggest that the antioxidant and anti-hyperglycemic actions of DD in a zebrafish diabetes model are likely associated with the regulation of the oxidative stress resistance and the insulin-signaling pathway and that could be related to the modulation at mRNA level of two important transcription factors, Nrf2 and FoxO.
Subject(s)
Antioxidants , Zebrafish , Animals , Antioxidants/pharmacology , Benzene Derivatives , Hypoglycemic Agents , Insulin , Organoselenium Compounds , Oxidation-Reduction , Oxidative Stress , Signal TransductionABSTRACT
Methylmercury (MeHg) and Ethylmercury (EtHg) are toxic to the central nervous system. Human exposure to MeHg and EtHg results mainly from the consumption of contaminated fish and thimerosal-containing vaccines, respectively. The mechanisms underlying the toxicity of MeHg and EtHg are still elusive. Here, we compared the toxic effects of MeHg and EtHg in Saccharomyces cerevisiae (S. cerevisiae) emphasizing the involvement of oxidative stress and the identification of molecular targets from antioxidant pathways. Wild type and mutant strains with deleted genes for antioxidant defenses, namely: γ-glutamylcysteine synthetase, glutathione peroxidase, catalase, superoxide dismutase, mitochondrial peroxiredoxin, cytoplasmic thioredoxin, and redox transcription factor Yap1 were used to identify potential pathways and proteins from cell redox system targeted by MeHg and EtHg. MeHg and EtHg inhibited cell growth, decreased membrane integrity, and increased the granularity and production of reactive species (RS) in wild type yeast. The mutants were predominantly less tolerant of mercurial than wild type yeast. But, as the wild strain, mutants exhibited higher tolerance to MeHg than EtHg. Our results indicate the involvement of oxidative stress in the cytotoxicity of MeHg and EtHg and reinforce S. cerevisiae as a suitable model to explore the mechanisms of action of electrophilic toxicants.
Subject(s)
Antioxidants/pharmacology , Ethylmercury Compounds/pharmacology , Methylmercury Compounds/pharmacology , Oxidative Stress/drug effects , Saccharomyces cerevisiae/drug effects , Oxidation-Reduction/drug effects , Saccharomyces cerevisiae/metabolismABSTRACT
Diabetes mellitus (DM) is a chronic metabolic disease that may comorbid with various psychiatric disorders, such as anxiety and depression. The search for effective therapeutics to alleviate hyperglycemia and complications resulting from DM is continuous. Here we investigate the effects of diphenyl diselenide (DD), an organoselenium compound with several pharmacological properties, in a zebrafish model of hyperglycemia. Fish were fed for 74â¯days with a diet containing 3â¯mg/Kg DD, a concentration chosen after experiments based in a dose-response curve (DD 1, 2 and 3â¯mg/Kg) that did not cause overt toxicity (mortality, weight loss and neurobehavioral deficits). In the last 14â¯days of the experimental period, fish were concomitantly exposed to a glucose solution (111â¯mM). Afterwards, blood glucose levels, brain selenium (Se) content, and behavioral analysis aiming to assess anxiety-like behaviors and locomotor/exploratory activities were performed. In the novel tank diving test, glucose decreased vertical exploration and fish spent less time in the lit area when tested in the light-dark test, suggesting increased anxiety-like behavior. Moreover, DD decreased blood glucose levels in hyperglycemic fish as well as prevented the development of anxiety-related symptoms. DD diet alone did not change glycemia and behavioral parameters, but increased Se levels in the brain without affecting the cellular viability. Collectively, our findings highlight the growing utility of this zebrafish hyperglycemia model as a valuable strategy for further research in DM field and neuroprotective approaches.
Subject(s)
Anxiety/etiology , Benzene Derivatives/administration & dosage , Hyperglycemia/complications , Hyperglycemia/psychology , Organoselenium Compounds/administration & dosage , Animals , Anxiety/diet therapy , Behavior, Animal/physiology , Blood Glucose/physiology , Brain/metabolism , Diet , Disease Models, Animal , Female , Glucose/administration & dosage , Hyperglycemia/diet therapy , Male , Selenium/metabolism , ZebrafishABSTRACT
ETNOPHARMACOLOGICAL RELEVANCE: Syzygium cumini (L.) Skeels is a plant widely used in folk medicine to treat diabetes mellitus (DM). The tea from its leaves is frequently used by diabetics for lowering hyperglycemia. There is a close relationship between DM and atherosclerosis, a chronic immuno-inflammatory disease, were the early stages encompass oxidative and glycative modifications in the structure of low density lipoprotein (LDL). AIM OF THIS STUDY: To investigate the potential protective effects of aqueous-leaf extract from Syzygium cumini (S.cExt) against CuSO4-induced oxidation and methylglyoxal (MG)-induced glycation of human LDL in vitro. MATERIALS AND METHODS: LDL oxidative changes were evaluated by measuring conjugated dienes (CD) formation, thiobarbituric acid reactive substances (TBARS) levels, quenching of tryptophan (Trp) fluorescence and structural modifications in LDL particle. In LDL glycated by MG (glyLDL), we determined the levels of fluorescent advanced glycation end products (AGEs) and mobility by agarose gel electrophoresis. RESULTS: S.cExt blocked oxidative events induced by CuSO4 in human LDL, plasma and serum. Fourier transform infrared spectroscopy (FT-IR) revealed that specific regions of apoB100 were oxidized by CuSO4 in human LDL and that S.cExt reduced these oxidations. Unlike, the increased AGEs levels and eletrophoretic mobility observed in LDL MG-glycated were not modified by S.cExt. CONCLUSION: The findings herein indicate that S.cExt could be tested in atherogenesis models as potential protective agent against LDL oxidation.