RESUMEN

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.

Asunto(s)

Atenolol , Conducta Animal , Estrés Oxidativo , Contaminantes Químicos del Agua , Pez Cebra , Animales , Atenolol/farmacología , Contaminantes Químicos del Agua/toxicidad , Estrés Oxidativo/efectos de los fármacos , Conducta Animal/efectos de los fármacos , Triptófano Hidroxilasa/metabolismo , Triptófano Hidroxilasa/genética , Factor Neurotrófico Derivado del Encéfalo/metabolismo

RESUMEN

The Ayurvedic medical system uses fruits of the Benincasa hispida plant to treat mental diseases, including schizophrenia. The goal of the current study was to assess the aqueous extract of B. hispida fruit's ability to relieve stress and anxiety induced in zebrafish models using neuropharmacological evaluation, which included determining behavioral parameters in tests such as the T-maze, open tank test (OTT), and light-dark preference test (LDPT). After measuring the zebrafish survival rate for 96 h, the LC50 was found to be 5 µg. AChE (acetylcholinesterase) inhibitory activity and the status of antioxidant enzymes (SOD, CAT, and LDH) were also used to evaluate the toxicity. Furthermore, the administration of the aqueous extract of B. hispida fruit increased the frequency of entry and duration of time spent in the bright section, suggesting a noteworthy reduction in levels of stress and anxiety. Additionally, the antistress and antianxiety activity was confirmed by the docking studies' mechanism of action, which involves the AChE receptor binding stability of the homogalactaconan molecule found in the aqueous extract of B. hispida fruit. Overall, the findings of this study demonstrated that the aqueous extract of B. hispida fruit is a viable therapeutic molecule for the creation of novel drugs and the treatment of stress since it has the therapeutic advantage of reversing the negative effects of stress and anxiety.

RESUMEN

Diabetes mellitus is a metabolic disorder characterized by inadequate insulin secretion and signaling dysfunction, leading to a vast spectrum of systemic complications. These complications trigger cascades of events that result in amyloid-beta plaque formation and lead to neurodegenerative disorders such as Alzheimer's. Repaglinide (REP) an insulinotropic agent, suppresses the down regulatory element antagonist modulator (DREAM) and enhances the ATF6 expression to provide neuroprotection following the DREAM/ATF6/apoptotic pathway. However, oral administration of REP for brain delivery becomes more complicated due to its physicochemical characteristics (high protein binding (>98%), low permeability, short half-life (∼1 h), low bioavailability). Therefore, to circumvent these problems, we develop a polymeric nanocarrier system (PNPs) by in-house synthesized di-block copolymer (PEG-PCL). PNPs were optimized using quality by design approach response surface methodology and characterized by particle size (112.53 ± 5.91 nm), PDI (0.157 ± 0.08), and zeta potential (-6.20 ± 0.82 mV). In vitro release study revealed that PNPs (∼70% in 48 h) followed the Korsmeyer-Peppas model with a Fickian diffusion release pattern, and in intestinal absorption assay PNPs showed increment of ∼1.3 folds compared of REP. Moreover, cellular studies confirmed that REP-loaded PNPs significantly enhance the cellular viability, uptake and reduce the peroxide-induced stress in neuroblastoma SHSY-5Y cells. Further, pharmacokinetic parameters of PNPs showed an increment in tmax (2.46-fold), and Cmax (1.25-fold) associated with REP. In the brain biodistribution study, REP loaded PNPs was sustained for 24 h whereas free REP sustained only for12 h. In DM induced neurodegenerative murine model, a significantly (p < 0.01) enhanced pharmacodynamic was observed in PNP treated group by estimating biochemical and behavioral parameters. Hence, oral administration of REP-loaded PNPs promotes efficient brain uptake and improved efficacy of REP in the diseased model.

Asunto(s)

Diabetes Mellitus , Nanopartículas , Enfermedades Neurodegenerativas , Ratones , Humanos , Animales , Portadores de Fármacos/química , Distribución Tisular , Polímeros/química , Nanopartículas/química , Tamaño de la Partícula

RESUMEN

Autism is a complex neurodevelopmental broad-spectrum disorder characterized by social interaction, and aberrant restrictive and repetitive behavior. The complex pathophysiology and unexplored drug targets make it difficult to standardize and validate the animal models of autism. The review was purposed for determining the benefits of younger animal models over adult models of autism. Similarly, animal models with respect to age, sex, body weight, number of animals used, along with autism inducing agents have been reviewed in this article. The differentiation of behavioral parameters has shown the benefits in the selection of younger animal models. Thus, we conclude that young and adolescence animal models of autism will be supporting for early detection and interventions with significant results.

Asunto(s)

Trastorno del Espectro Autista , Trastorno Autístico , Animales , Humanos , Modelos Animales de Enfermedad , Cognición

RESUMEN

The aim of the present study was to evaluate the anti-glioma activity of 3-(4-fluorobenzyl)-5-(4-methoxybenzylidene)thiazolidine-2,4-dione (AV23) in a preclinical model of glioblastoma, as well as behavioral parameters and toxicological profile. The implantation of C6 cells in the left striatum of male Wistar rats was performed by stereotaxic surgery. After recovery, animals were treated with vehicle (canola oil) or AV23 (10 mg/kg/day) intragastrically for 15 days. It was found that AV23 reduced tumor volume by 90%. Serum biochemical parameters such as triglycerides, cholesterol, HDL-cholesterol, LDL-cholesterol, albumin, aspartate aminotransferase, urea, creatinine and total proteins were not changed; however, there was a slight increase in alanine aminotransferase. The compound AV23 reverted the hypoglycemia and the reduction in body weight caused by glioblastoma. Additionally, AV23 was able to revert the reduction of locomotion caused by the tumor implantation. Therefore, the compound AV23 can be considered a promising candidate in the treatment of glioblastoma.

Asunto(s)

Glioblastoma , Tiazolidinedionas , Animales , Glioblastoma/tratamiento farmacológico , Masculino , Ratas , Ratas Wistar , Tiazolidinas

RESUMEN

Indoor exposure to organic flame retardants (FRs) has raised extensive concern due to associated adverse health effects. Indoor-exposure induced daily intakes of six widely used FRs individually ranged 0.002-611 ng/day and 0.02-463 ng/day, respectively, for adults and 2-6-year-old children; and resulting internal exposure levels ranged 0.1-159 and 2.1-4500 ng/g lipid, respectively. A proportion of 0.001-5.9% and 0.006-10.3% of individual FRs emitted into indoor air ultimately entered bodies of adults and children respectively. Tris(2-chloroisopropyl)phosphate dominated in emissions, whilst 2-ethylhexyl-2,3,4,5-tetrabromobenzoate dominated in human bodies. Hand-to-mouth contact was the most important exposure pathway for less volatile FRs including most brominated FRs, whilst inhalation was the predominant intake pathway of tris(2-chloroisopropyl)phosphate. Relative importance of 29 environmental, behavioral and physiological parameters was ranked to explore key drivers influencing exposure and accumulation of FRs in humans. Results suggested that frequent bathing and handwashing can reduce exposure effectively, especially for children. Bodyweight and lipid fraction were only positively related to internal accumulation and body-weight-normalized concentrations of compounds with low metabolic rates (half-lives ≥103 h) in humans. Our findings help control indoor exposure to FRs and are supportive of human exposome studies in the future.

Asunto(s)

Contaminación del Aire Interior , Retardadores de Llama , Adulto , Contaminación del Aire Interior/análisis , Niño , Polvo/análisis , Exposición a Riesgos Ambientales , Monitoreo del Ambiente , Retardadores de Llama/análisis , Éteres Difenilos Halogenados/análisis , Humanos , Lípidos , Organofosfatos/análisis , Compuestos Organofosforados/análisis , Fosfatos/análisis

RESUMEN

The fungicide difenoconazole, widely used to reduce the negative impacts of fungi diseases on areas with intensive farming, can reach freshwater systems causing deleterious effects on nontarget organisms. The acute and chronic toxicity of a commercial formulation containing 250 g L-1 of difenoconazole (Prisma®) as the active ingredient was assessed in the freshwater planarian Girardia tigrina. The endpoints evaluated were feeding rate, locomotion, regeneration, and sexual reproduction of planarians. The estimated 48 h LC50 of the commercial formulation on planarians expressed as the concentration of the active ingredient difenoconazole was 47.5 mg a.i.L-1. A significant decrease of locomotion (LOEC = 18.56 mg a.i.L-1), delayed regeneration (LOEC = 9.28 mg a.i.L-1), and sexual reproduction impairment, i.e., decreased fecundity and fertility rates (LOEC ≤ 1.16 mg a.i.L-1) were observed on planarians exposed to sublethal concentrations of the formulation. This study demonstrated the importance of using reproductive, physiological, and behavioral parameters as more sensitive and complementary tools to assess the deleterious effects induced by a commercial formulation of difenoconazole on a nontarget freshwater organism. The added value and importance of our research work, namely, the impairment of sexual reproduction of planarians, contributes to the development of useful tools for ecotoxicology and highlights the fact that those tools should be developed as guidelines for testing of chemicals. Our results showed that the use of reproductive parameters of Girardia tigrina would help to complement and achieve a better assessment of the risk posed by triazole fungicides to freshwater ecosystems.

Asunto(s)

Planarias , Contaminantes Químicos del Agua , Animales , Dioxolanos , Ecosistema , Ecotoxicología , Reproducción , Triazoles/toxicidad , Contaminantes Químicos del Agua/toxicidad

RESUMEN

Eutrophication models are of great importance and are valuable tools for the development of policy and legislation. However, the parameter uncertainty and substantial computational cost lead to difficulties in decision-making, especially for complex models with multiple indicators. A multicriteria uncertainty analysis and parameter estimation (MUAPE) method, which selected behavioral parameters combined with Pareto domination and simultaneously obtained acceptable values for modeling by the maximum likelihood concept and kernel density estimation, was shown. This method, which did not assign thresholds and weights, was applied to analyze the uncertainty of the Chaohu Lake eutrophication model and estimate parameters. The results of the behavioral parameters were compared using different criterion sets, the relative error (RE) and the root mean square error (RMSE), and the results showed little discrepancy in terms of the effects on parameter uncertainty represented by the marginal probability density. The uncertainties of the parameters related to algal kinetics (i.e., BMR, PM, and KESS) were smaller than those of nutrient- and temperature-related parameters (i.e., KDN, Nitm, KTB, and KTHDR) for both sets of criteria. However, the reduction in the joint uncertainty of the two parameters was greater when RE was used than when RMSE was used. The acceptable values for the key parameters of the Chaohu Lake eutrophication model were also obtained by the RE criterion. The results strongly agreed with the observed values, and parameters could be applied for model prediction. This result indicated that the combination method was not only practical for reducing parameter uncertainty but also useful for determining parameter values. This method provides a basis for multicriteria uncertainty analysis and parameter estimation in eutrophication modeling.

Asunto(s)

Monitoreo del Ambiente , Lagos , China , Eutrofización , Incertidumbre

RESUMEN

The objective of this study was to evaluate the effects of the inclusion of different levels of licuri cake on the consumption of dry matter and nutrients and ingestive behavior of feedlot crossbred steers. Forty-four crossbred steers with an average age of 24 months and a mean live weight of 358.19 ± 41.57 kg were used in the study. The animals were aleatorically distributed in a completely randomized design made up of four treatments, with 11 animals used per treatment: the control treatment (without the inclusion of licuri cake in the diet) and treatment with the inclusion levels of 8.5, 17, and 25.5% of licuri cake, respectively, in the total dry matter of the diet. The inclusion of licuri cake influenced the intake of dry matter, crude protein, ether extract, neutral detergent fiber corrected for ash and protein, and non-fibrous carbohydrates corrected for ash and protein, each of them showing quadratic behavior. There was an effect of the tested diets on the time spent on food intake and number of idle periods, which presented a quadratic effect, with maximum and minimum values obtained for the inclusion levels of the licuri cake of 16.92% and 11.00%, respectively. There was no effect of the tested diets on the time spent on rumination and idleness. The feed efficiency of the dry matter, the duration of the feeding period, and the duration of the idleness period were influenced by the inclusion of the licuri tart in the diet, presenting a linear decreasing effect. There was an increasing linear effect for the number of feeding periods and the duration of rumination periods. Given the results obtained, it can be concluded that the licuri cake changes the consumption and behavioral parameters of feedlot steers, being recommended its use in up to 8.5% of inclusion in the total dry matter of the diet.

Asunto(s)

Alimentación Animal/estadística & datos numéricos , Arecaceae , Bovinos , Dieta/veterinaria , Conducta Alimentaria , Alimentación Animal/análisis , Animales , Fibras de la Dieta , Ingestión de Energía , Masculino , Nutrientes

RESUMEN

Adverse events in early life have been related to a maladaptive stress response during adulthood, which could predispose individuals to psychiatric and physiological disorders. The purpose of this work was to study the implications of repeated maternal separation (RMS) plus a physical stressor (cold stress), voluntary ethanol consumption and plasmatic levels of corticosterone (Cor) via conflict behavior tests. To this aim, pups were separated daily from their mothers for one hour and subjected to cold stress (4 °C) between postnatal days (PD) 2 and 20. Control groups were left undisturbed with their mothers. Afterwards, all groups were exposed to voluntary ethanol (6%) or dextrose (1%) intake for 7 days. After a 30-day period of environmental enrichment (EE), the animals were again exposed to the voluntary intake protocol for 7 days. At 66 days, they were subjected to different conflict tests. Thereafter, rats were sacrificed by decapitation and blood trunk was collected to determine plasma corticosterone levels. We demonstrated that early RMS increased both voluntary alcohol intake and Cor levels. Moreover, young adult animals showed excessive activity in conflict tests. Whereas in animals exposed to a non-pharmacological treatment, known as environmental enrichment (EE), the effects previously obtained were reversed and/or prevented. In summary, we can conclude that the combination of maternal separation in early life plus cold stress increase both the voluntary exposure to alcohol and disruptive behaviors. This is a risk factor for the development of chronic diseases such as alcoholism and long-term depression. However, we found that an enriched environment may have a beneficial effect with respect to alcohol intake and aggressive behaviors.

Asunto(s)

Consumo de Bebidas Alcohólicas/sangre , Ansiedad/sangre , Corticosterona/sangre , Privación Materna , Estrés Psicológico/sangre , Animales , Conducta Exploratoria/fisiología , Femenino , Vivienda para Animales , Masculino , Actividad Motora/fisiología , Ratas , Ratas Wistar

RESUMEN

This study aimed to investigate the effects of Coriandrum sativum aqueous extract (CSAE) on the rat progeny of mothers exposed to methylmercury (MeHg). The presence of bioactive compounds and CSAE's antioxidant capacity been evaluated, and the offspring were assessed for their total mercury levels, motor behavioral parameters and oxidative stress in the cerebellum. The analysis of the bioactive compounds revealed significant amounts of polyphenols, flavonoids, and anthocyanins, as well as a variety of minerals. A DPPH test showed the CSAE had important antioxidant activity. The MeHg + CSAE group performed significantly better spontaneous locomotor activity, palmar grip strength, balance, and motor coordination in behavioral tests compared the MeHg group, as well as in the parameters of oxidative stress, with similar results to those of the control group. The MeHg + CSAE group also had significantly reduced mercury levels in comparison to the MeHg group. Based on the behavioral tests, which detected large locomotor, balance, and coordination improvements, as well as a reduction in oxidative stress, we conclude that CSAE had positive functional results in the offspring of rats exposed to MeHg.

Asunto(s)

Coriandrum/química , Intoxicación del Sistema Nervioso por Mercurio/prevención & control , Compuestos de Metilmercurio/toxicidad , Neuroprotección/efectos de los fármacos , Fármacos Neuroprotectores/uso terapéutico , Extractos Vegetales/uso terapéutico , Animales , Cerebelo/efectos de los fármacos , Femenino , Peroxidación de Lípido/efectos de los fármacos , Locomoción/efectos de los fármacos , Masculino , Exposición Materna , Actividad Motora/efectos de los fármacos , Trastornos del Movimiento/prevención & control , Fármacos Neuroprotectores/aislamiento & purificación , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/aislamiento & purificación , Hojas de la Planta/química , Tallos de la Planta/química , Embarazo , Ratas , Especies Reactivas de Oxígeno/metabolismo

RESUMEN

Changes in the blood cytokine profile of rats with different behavioral activity were evaluated in various periods after stress exposure on the model of 24-h immobilization. Behaviorally active animals exhibited only a tendency to a change in the concentration of study cytokines in the dynamics after experimental stress. Stress exposure in passive specimens was accompanied by a decrease in the content of pro- and anti-inflammatory cytokines. These changes were most pronounced at the early stages of the post-stress period and persisted until the end of observations. After a single exposure to long-term immobilization, cytokine level in the peripheral blood of behaviorally passive animals was much lower than in active rats. Variations in immune indexes of mammals depend on the initial parameters of their behavior and duration of the post-stress period. Differences in the blood cytokine profile during negative emotiogenic exposures in passive and active rats are probably related to the specifics of immune reactivity in specimens with various sensitivities to stress.

Asunto(s)

Conducta Animal/fisiología , Citocinas/sangre , Estrés Psicológico/sangre , Estrés Psicológico/fisiopatología , Enfermedad Aguda , Animales , Antiinflamatorios/sangre , Mediadores de Inflamación/sangre , Masculino , Ratas , Ratas Wistar , Factores de Tiempo

RESUMEN

OBJECTIVE: Ficus racemosa (FR) is one of the herbs mentioned in the scriptures of the Ayurveda as Udumbara with high medicinal value. The objective of this study was to estimate the protective effect of FR against streptozotocin (STZ) induced diabetic neuropathy with neurodegeneration (DNN). MATERIALS AND METHODS: Diabetes was induced in Wistar rats with STZ and were divided into six groups namely diabetic vehicle control, FR (four) and glibenclamide (one) treated rats; while one group was of normal control rats. After the 4(th) week of diabetes, induction treatment was started for further 28 days (5(th) to 8(th) week) with FR aqueous extract (250 mg/kg and 500 mg/kg) and ethanolic extract (200 mg/kg and 400 mg/kg). Investigation of DNN was carried out through biochemical and behavioral parameter assessment in rats. RESULTS: Study showed a significant fall in glycosylated hemoglobin (HbA1c) and blood glucose level by the treatment of FR in diabetic rats. Antioxidant potential of FR showed a great rise in superoxide dismutase, catalase content and reduction observed in serum nitrite level; while significant fall in lipid peroxidation level and of C-reactive protein was observed in FR treated diabetic rats. Further FR treated diabetic rats also showed marked improvement in tail flick latency, pain threshold, the rise in locomotion and fall latency period. CONCLUSION: Treatment with FR shows protection in the multiple pathways of DNN by improving blood glucose, HbA1c, biochemical, and behavioral parameters, which suggest the protective role of FR in the reversal of DNN.

Asunto(s)

Antioxidantes/uso terapéutico , Neuropatías Diabéticas/prevención & control , Ficus/química , Hipoglucemiantes/uso terapéutico , Fármacos Neuroprotectores/uso terapéutico , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/uso terapéutico , Animales , Antioxidantes/administración & dosificación , Antioxidantes/efectos adversos , Antioxidantes/aislamiento & purificación , Conducta Animal/efectos de los fármacos , Diabetes Mellitus Experimental/complicaciones , Neuropatías Diabéticas/sangre , Neuropatías Diabéticas/metabolismo , Relación Dosis-Respuesta a Droga , Etnofarmacología , Hemoglobina Glucada/análisis , Hiperglucemia/prevención & control , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/efectos adversos , Hipoglucemiantes/aislamiento & purificación , Peroxidación de Lípido/efectos de los fármacos , Masculino , Medicina Ayurvédica , Fármacos Neuroprotectores/administración & dosificación , Fármacos Neuroprotectores/efectos adversos , Fármacos Neuroprotectores/aislamiento & purificación , Corteza de la Planta/química , Extractos Vegetales/administración & dosificación , Extractos Vegetales/aislamiento & purificación , Tallos de la Planta/química , Distribución Aleatoria , Ratas Wistar , Pruebas de Toxicidad Aguda

RESUMEN

Copaiba oil, extracted from Copaifera multijuga Hayne, Fabaceae, is widely used for medicinal purposes, especially to treat inflammatory processes. However, there is no report regarding its effect on reproductive performance after used in repeated doses orally. The present study evaluated the effects of the oral administration of Copaiba oil (at doses of 200, 500 or 2500 mg/kg) or water (control) for eight weeks in male Wistar rats. Treated males mated untreated females, and parameters as fertility rates, absolute and relative mass of accessory sexual organs and histology and development of the offspring were evaluated. Chemical analysis revealed the presence of 22 components accounting for 99.11% of the Copaiba oil. The main compounds identified were sesquisterpenes. The reproductive toxicology results indicate that there was no difference between the treated groups compared with the control group in any of the parameters, suggesting that the oral treatment with C. multijuga oil for eight weeks does not affect reproductive performance of male Wistar rats.