RESUMEN
ß-carotene-loaded nanoparticles improves absorption by increasing bioavailability. The Drosophila melanogaster model of Parkinson's disease must be helpful in investigating potential neuroprotective effects. Four groups of four-day-old flies were exposed to: (1) control; (2) diet containing rotenone (500 µM); (3) ß-carotene-loaded nanoparticles (20 µM); (4) ß-carotene-loaded nanoparticles and rotenone for 7 days. Then, the percentage of survival, geotaxis tests, open field, aversive phototaxis and food consumption were evaluated. At the end of the behaviors, the analyses of the levels of reactive species (ROS), thiobarbituric acid reactive substances (TBARS), catalase (CAT) and superoxide dismutase (SOD) activity was carried out, as well as an evaluation of the levels of dopamine and acetylcholinesterase (AChE) activity, in the head of flies. Nanoparticles loaded with ß-carotene were able to improve motor function, memory, survival and also restored the oxidative stress indicators (CAT, SOD, ROS and TBARS), dopamine levels, AChE activity after exposure to rotenone. Overall, nanoparticles loaded with ß-carotene showed significant neuroprotective effect against damage induced by the Parkinson-like disease model, emerging as a possible treatment. Overall, ß-carotene-loaded nanoparticles presented significant neuroprotective effect against damage induced by model of Parkinson-like disease, emerging as a possible treatment.
Asunto(s)
Nanopartículas , Fármacos Neuroprotectores , Enfermedad de Parkinson , Animales , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/prevención & control , Drosophila melanogaster , beta Caroteno/farmacología , Antioxidantes/farmacología , Antioxidantes/metabolismo , Dopamina , Rotenona , Especies Reactivas de Oxígeno , Fármacos Neuroprotectores/farmacología , Sustancias Reactivas al Ácido Tiobarbitúrico , Acetilcolinesterasa/metabolismo , Estrés Oxidativo , Superóxido Dismutasa/metabolismo , Modelos Animales de EnfermedadRESUMEN
Non-motor alterations such as anxiety and memory deficit may represent early indications of Parkinson's disease (PD), and therapeutic strategies that reduce non-motor alterations are promising alternatives for the treatment. Therefore, the search for natural compounds that act on motor and non-motor complications is highly relevant. In this sense, we demonstrated the role of hesperidin (Hsd) as a citrus flavonoid and its pharmacological properties as an antioxidant and neuroprotective agent. Our objective was to evaluate Hsd in developing motor and non-motor alterations in a Drosophila melanogaster model of Parkinson-like disease induced by iron (Fe) exposure. The flies were divided into six groups: control, Hsd (10 µM), L-dopa (positive control, 1 mM), Fe (1 mM), Fe + Hsd, and Fe + L-dopa. Motor coordination tests, memory assessment through aversive phototaxy, and anxiety-like behaviors characterized in flies, such as grooming and aggressiveness, were performed. The Hsd attenuated motor and non-motor alterations, such as motor coordination, memory deficits and anxiety-like behaviors, attenuated monoaminergic deficits, and lowered Fe levels in the head of flies. In addition, Hsd prolonged the life of the flies, thereby standing out from the L-dopa-treated group. Thus, Hsd can protect the dopaminergic system from insults caused by Fe, preventing non-motor alterations in PD; Hsd also reduced Fe levels in the flies' heads, suggesting that iron chelation may represent an important mechanism of action, in addition to its antioxidant action.
Asunto(s)
Hesperidina , Enfermedad de Parkinson , Animales , Modelos Animales de Enfermedad , Dopamina , Drosophila melanogaster , Hesperidina/farmacología , Hesperidina/uso terapéutico , Levodopa , Enfermedad de Parkinson/tratamiento farmacológicoRESUMEN
Environmental factors are involved in the pathogenesis of neurodevelopmental disorders in addition to genetic factors. In this sense, we demonstrated here that the embryonic exposure of Drosophila melanogaster to Bisphenol A (BPA) 1 mM resulted in changes in development, behavior, and biochemical markers punctuated below. BPA did not alter the oviposition and viability of the eggs, however, it was evidenced a decrease in the rate of pupal eclosion and life span of the hatched flies of the generation filial 1 (F1). F1 flies also developed behavioral changes such as incompatibility in the social interaction between them, and hyperactivity demonstrated by increased locomotion in open field tests, increased grooming, and aggression episodes. Furthermore, decreases in dopamine levels and tyrosine hydroxylase activity have also been observed in flies' heads, possibly related to oxidative damage. Through analyzes of oxidative stress biomarkers, carried out on samples of flies' heads, we observed an increase in malondialdehyde and reactive species, decrease in the activity of the superoxide dismutase and catalase, which possibly culminated in the reduction of cell viability. Thus, it is important to emphasize that BPA developed atypical behaviors in Drosophila melanogaster, reinforce the importance of the environmental factor in the development of neurobehavioral diseases.
Asunto(s)
Conducta Animal/efectos de los fármacos , Compuestos de Bencidrilo/toxicidad , Dopamina/metabolismo , Drosophila melanogaster/efectos de los fármacos , Fenoles/toxicidad , Animales , Catalasa/metabolismo , Dopamina/fisiología , Drosophila melanogaster/embriología , Drosophila melanogaster/crecimiento & desarrollo , Femenino , Fertilidad/efectos de los fármacos , Glutatión Transferasa/metabolismo , Masculino , Prueba de Campo Abierto/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Pupa/efectos de los fármacos , Superóxido Dismutasa/metabolismo , Tirosina/metabolismo , Tirosina 3-Monooxigenasa/efectos de los fármacos , Tirosina 3-Monooxigenasa/metabolismoRESUMEN
Neurodevelopmental disorders, such as Autism Spectrum Disorder (ASD) and Attention Deficit Hyperactivity Disorder (ADHD) are responsible for behavioral deficits in children. Imidacloprid is a nicotinic acetylcholine receptor agonist, capable of causing behavioral changes in Drosophila melanogaster, similar to the ADHD-like phenotypes. We assess whether behavioral damage induced by imidacloprid exposure in Drosophila melanogaster is associated with neurochemical changes and whether these changes are similar to those observed in neurodevelopmental disorders such as ASD and ADHD. The fruit flies were divided into four groups, exposed to either a standard diet (control) or a diet containing imidacloprid (200, 400 or 600 ρM) and allowed to mate for 7 days. After hatching, the progeny was subjected to in vivo and ex vivo tests. The ones exposed to imidacloprid showed an increase in hyperactivity, aggressiveness, anxiety and repetitive movements, as well as, a decrease in social interaction. Furthermore, exposure to imidacloprid decreased dopamine levels, cell viability and increased oxidative stress in the flies' progeny. These results demonstrated that the behavioral damage induced by imidacloprid exposure involves a reduction in dopamine levels and oxidative stress and that these neurochemical changes are in line with the events that occur in ASD and ADHD-like phenotypes in other models.
Asunto(s)
Dopamina/metabolismo , Insecticidas/toxicidad , Neonicotinoides/toxicidad , Trastornos del Neurodesarrollo/inducido químicamente , Trastornos del Neurodesarrollo/metabolismo , Nitrocompuestos/toxicidad , Estrés Oxidativo/efectos de los fármacos , Animales , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Relación Dosis-Respuesta a Droga , Drosophila melanogaster , Femenino , Masculino , Estrés Oxidativo/fisiología , Interacción Social/efectos de los fármacosRESUMEN
Iron (Fe) is used in various cellular functions, and a constant balance between its uptake, transport, storage, and use is necessary to maintain its homeostasis in the body. Changes in Fe metabolism with a consequent overload of this metal are related to neurological changes and cover a broad spectrum of diseases, mainly when these changes occur during the embryonic period. This work aimed to evaluate the effect of exposure to Fe overload during the embryonic period of Drosophila melanogaster. Progenitor flies (male and female) were exposed to ferrous sulfate (FeSO4) for ten days in concentrations of 0.5, 1, and 5 âmM. After mating and oviposition, the progenitors were removed and the treatment bottles preserved, and the number of daily hatches and cumulative hatching of the first filial generation (F1) were counted. Subsequently, F1 flies (separated by sex) were subjected to behavioral tests such as negative geotaxis test, open field test, grooming, and aggression test. They have evaluated the levels of dopamine (DA), serotonin (5-HT), octopamine (OA), tryptophan and tyrosine hydroxylase (TH), acetylcholinesterase, reactive species, and the levels of Fe in the progenitor flies and F1. The Fe levels of F1 flies are directly proportional to what is incorporated during the period of embryonic development; we also observed a delay in hatching and a reduction in the number of the hatch of F1 flies exposed during the embryonic period to the 5mM Fe diet, a fact that may be related to the reduction of the cell viability of the ovarian tissue of progenitor flies. The flies exposed to Fe (1 and 5 âmM) showed an increase in locomotor activity (hyperactivity) and a significantly higher number of repetitive movements. In addition to a high number of aggressive encounters when compared to control flies. We can also observe an increase in the levels of biogenic amines DA and 5-HT and an increase in TH activity in flies exposed to Fe (1 and 5 âmM) compared to the control group. We conclude that the hyperactive-like behavior demonstrated in both sexes by F1 flies exposed to Fe may be associated with a dysregulation in the levels of DA and 5-HT since Fe is a cofactor of TH, which had its activity increased in this study. Therefore, more attention is needed during the embryonic development period for exposure to Fe overload.
Asunto(s)
Drosophila melanogaster/embriología , Hipercinesia/fisiopatología , Sobrecarga de Hierro/embriología , Animales , Conducta Animal/fisiología , Aminas Biogénicas/metabolismo , Aminas Biogénicas/fisiología , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Femenino , Expresión Génica/genética , Regulación del Desarrollo de la Expresión Génica/genética , Hipercinesia/etiología , Hierro/metabolismo , Hierro/fisiología , Hierro/toxicidad , Sobrecarga de Hierro/metabolismo , Sobrecarga de Hierro/fisiopatología , Locomoción/efectos de los fármacos , Masculino , Exposición Materna , Actividad Motora/efectos de los fármacos , Oxidación-Reducción , Exposición PaternaRESUMEN
Parkinson's is a neurodegenerative disease, characterized by the loss of dopaminergic neurons, cholinergic alterations and oxidative damages. Lutein is widely known by its antioxidants properties. In the present study, we investigated whether lutein-loaded nanoparticles protects against locomotor damage and neurotoxicity induced by Parkinson's disease model in Drosophila melanogaster, as well as possible mechanisms of action. First, the nanoparticles were characterized by physicochemical methods, demonstrating that water affinity was improved by the encapsulation of lutein into the polymeric encapsulant matrix. The fruit flies of 1-4 days old were divided into four groups and exposed to a standard diet (control), a diet containing either rotenone (500 µM), lutein-loaded nanoparticles (6 µM) or rotenone (500 µM) and lutein-loaded nanoparticles (6 µM) for 7 days. The survival percentage was assessed, the flies were submitted to negative geotaxis, open field tasks and the determination of dopamine levels, tyrosine hydroxylase (TH) and acetylcholinesterase activities and oxidative stress indicators (superoxide dismutase, catalase, thiobarbituric acid reactive substances and glutathione S-transferase) were carried out. The exposure to lutein-loaded nanoparticles protected against locomotor damage and the decrease survival rate induced by rotenone, besides, it restored the dopamine levels, TH and acetylcholinesterase activities and oxidative stress indicators. These results provide evidence that lutein-loaded nanoparticles are an alternative treatment for rotenone-induced damage, and suggest the involvement of dopaminergic and cholinergic system and oxidative stress.
Asunto(s)
Neuronas Colinérgicas/efectos de los fármacos , Neuronas Dopaminérgicas/efectos de los fármacos , Drosophila melanogaster/efectos de los fármacos , Luteína/farmacología , Nanopartículas/química , Estrés Oxidativo/efectos de los fármacos , Enfermedad de Parkinson/tratamiento farmacológico , Acetilcolinesterasa/metabolismo , Animales , Neuronas Colinérgicas/metabolismo , Modelos Animales de Enfermedad , Dopamina/metabolismo , Neuronas Dopaminérgicas/metabolismo , Drosophila melanogaster/metabolismo , Enfermedades Neurodegenerativas/tratamiento farmacológico , Enfermedades Neurodegenerativas/metabolismo , Síndromes de Neurotoxicidad/tratamiento farmacológico , Síndromes de Neurotoxicidad/metabolismo , Enfermedad de Parkinson/metabolismoRESUMEN
Manganese (Mn) is an essential element that, in excess, seems to be involved in the development of different neurodegenerative conditions. Gamma-oryzanol (Ory) was previously reported to possess antioxidant and neuroprotective properties. Thus, we conducted this study to test the hypothesis that Ory can also protect flies in an Mn intoxication model. Adult wild-type flies were fed over 10 days with Mn (5 mM) and/or Ory (25 µM). Flies treated with Mn had a decrease in locomotor activity and a higher mortality rate compared to those in controls. Mn-treated flies also had a significant increase in acetylcholinesterase (AChE) activity, in Mn accumulation and in oxidative stress markers. Moreover, flies treated with Mn exhibited a significant decrease in dopamine levels and in tyrosine hydroxylase activity, as well as in mitochondrial and cellular viability. Particularly important, Ory protected against mortality and avoided locomotor and biochemical changes associated with Mn exposure. However, Ory did not prevent the accumulation of Mn. The present results support the notion that Ory effectively attenuates detrimental changes associated with Mn exposure in Drosophila melanogaster, reinforcing its neuroprotective action/potential.
Asunto(s)
Drosophila melanogaster , Manganeso , Animales , Antioxidantes , Manganeso/toxicidad , Estrés Oxidativo , FenilpropionatosRESUMEN
Chronic unpredictable mild stress (CUMS) is a valid model for inducing depression-like symptoms in animal models, causing predictive behavioral, neurochemical, and physiological responses to this condition. This work aims to evaluate the possible antidepressant effect of γ-oryzanol (ORY) in the CUMS-induced depressive model in male Drosophila melanogaster. We will use the CUMS protocol to continue the study previously conducted by our research group, mimicking a depressive state in these insects. Male flies were subjected to various stressors according to a 10-day randomized schedule and concomitantly treated with ORY or fluoxetine (FLX). After the experimental period, in vivo behavioral tests were performed (open field, forced swimming, aggressiveness test, mating test, male virility, sucrose preference index and light/dark test) and ex vivo analyses measuring serotonin (5HT), dopamine (DA), octopamine (OCT) levels and body weight. We report here that ORY-treated flies and concomitant exposure to CUMS did not exhibit obvious behaviors such as prolonged immobility or increased aggressive behavior, reduced male mating and virility behavior, and anxiolytic behavior, in contrast to ORY, not altering sucrose preference and body weight flies exposed to CUMS. ORY effectively prevented 5HT and OCT reduction and partially protected against DA reduction. The data presented here are consistent and provide evidence for the use of ORY as a potential antidepressant compound.Lay SummaryFlies treated with ORY and concomitant exposure to CUMS did not exhibit obvious depressive-like behaviors, such as prolonged immobility in the FST or increased aggressive behavior, or reduced mating behavior, male virility, or anxiolytic behavior. ORY did not change the preference for sucrose and body weight of flies, about the levels of monoamines in the heads of flies, ORY was effective in preventing the reduction of 5HT and OCT, and we had partial protection of ORY for reducing the levels of DA.
Asunto(s)
Depresión , Drosophila melanogaster , Animales , Antidepresivos/farmacología , Conducta Animal , Depresión/tratamiento farmacológico , Modelos Animales de Enfermedad , Hipocampo , Masculino , Fenilpropionatos , Estrés PsicológicoRESUMEN
Phytoremediation is a technique that reduces the impact and environmental toxicity of toxic agents. Plectranthus neochilus, a species of aromatic plant, has already promoted phytoremediation of the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D). In addition, it was unclear whether the degradation of 2,4-D alone allows for a non-toxic environment (decontamination efficiency). Therefore, the aim of the present study was to verify the changes of the volatile compounds and concentrated essential oil of P. neochilus after phytoremediation of 2,4-D and the subsequent antibacterial activity of this essential oil concentrate. In addition, the toxicity of the plant's tea and the aqueous medium (waste) after the decontamination of 2,4-D was analyzed. The exposure to 2,4-D did not cause many changes in the volatile compounds, nor in the essential oil concentrate from the plant. Therefore, this essential oil concentrate can be used as an antimicrobial after phytoremediation. Regarding the use of this plant in tea form, it was found to be unsafe, even after phytoremediation, as this tea was toxic to the Drosophila melanogaster model (death of up to 100% of flies). The aqueous medium after 2,4-D phytoremediation became less toxic than the initial one (bioassays with Artemia salina and Allium cepa in the waste groups). However, the efficiency of phytoremediation with this plant must be improved. Therefore, we are performing new studies with P. necohilus and 2,4-D in aqueous medium.
Asunto(s)
Aceites Volátiles , Plectranthus , Ácido 2,4-Diclorofenoxiacético/toxicidad , Animales , Biodegradación Ambiental , Drosophila melanogasterRESUMEN
The pathogenesis of Parkinson's disease has not been fully clarified yet but its cause is known to be multifactorial. One of these factors is oxidative stress induced by exposure to environmental toxifiers. We studied the effect of Bisphenol A (BPA) at concentrations of 0.5 mM and 1 mM, the concentration of 1 mM corresponding to Lowest Observed Adverse Effect Level (LOAEL) for humans in adult Drosophila melanogaster. The BPA induced oxidative stress was established by increased levels of malondialdehyde, reactive species, and decreased activity of the antioxidant enzymes superoxide dismutase and catalase, and detoxificant enzyme glutathione-S-transferase. Associated with oxidative stress, there was a reduction of acetylcholinesterase activity and a reduction of dopamine levels, which are related to the decreased locomotion activity as observed in negative geotaxis, open field and equilibrium behaviors in group exposed to 1 mM of BPA. Oxidative stress also impaired mitochondrial and cellular metabolic activity in the head causing an increase in the mortality of flies exposed to both BPA concentrations. Therefore, BPA induced Parkinsonian-like changes in flies and it is possible that the oxidative stress is closely related to this effect, providing new insights for future studies.
Asunto(s)
Compuestos de Bencidrilo/toxicidad , Drosophila melanogaster/efectos de los fármacos , Drosophila melanogaster/crecimiento & desarrollo , Enfermedad de Parkinson/etiología , Fenoles/toxicidad , Animales , Catalasa/metabolismo , Modelos Animales de Enfermedad , Dopamina/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Femenino , Glutatión Transferasa/metabolismo , Humanos , Masculino , Malondialdehído/metabolismo , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Nivel sin Efectos Adversos Observados , Estrés Oxidativo/efectos de los fármacos , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/fisiopatología , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/metabolismoRESUMEN
During the neonatal period, the brain is susceptible to external influences. Exposure to stressful events during this phase of life influences brain development and impacts adult life. In animals, the maternal deprivation (MD) model is effective in mimicking stress in the early stages of development. In contrast, physical exercise seems to be able to prevent deficits in memory consolidation. Although the effects of chronic exercise in cognition are already well established, little is known about the effects of acute aerobic exercise. Here, male Wistar rats divided into deprived (MD) and nondeprived (NMD) rats were submitted to the object recognition (OR) memory test. Immediately after OR training, some of the rats were submitted to a single aerobic exercise session for 30 minutes. Memory consolidation and persistence were evaluated by retention tests performed 24 h and 7, 14, and 21 days after OR training. We show that a single physical exercise session is able to modulate learning by promoting memory consolidation and persistence in rats with cognitive deficits induced by MD. Hippocampal dopamine levels, measured by HPLC, were not altered after OR training in rats that performed and in rats that did not perform an exercise session; on the other hand, while OR training promoted increase of hippocampal norepinephrine in NMD rats, the MD rats did not present this increase, regardless of the practice or not of exercise.
Asunto(s)
Encéfalo/fisiología , Privación Materna , Trastornos de la Memoria/fisiopatología , Condicionamiento Físico Animal , Animales , Reacción de Prevención/fisiología , Cognición/fisiología , Conducta Exploratoria/fisiología , Femenino , Hipocampo/efectos de los fármacos , Consolidación de la Memoria/fisiología , Ratas Wistar , Reconocimiento en PsicologíaRESUMEN
The possible phytoremediation capacity of Plectranthus neochilus (boldo) exposed to the commercial pesticide (Aminol) in soil and water through consecutive extractions (days interval) was evaluated. After the exposure period, tea leaves from the plant were analyzed in terms of the presence of 2,4-D, total antioxidant capacity (DPPH), concentration of total polyphenols and flavonoids for plants exposed to soil and water. In water, 2,4-D remained up to 67% in the 60 days of experiment in the control group, which provided the use of two treatment groups with the plant (one group of plants for 30 days and another group in the remaining 30 days in the same system), thus, a decontamination up to 49% of the 2,4-D was obtained in this system with water. In both experiments (soil and water) the 2,4-D was not detected in tea leaves, the reduction of the antioxidant activity, polyphenols and flavonoids of plants exposed to the herbicide was also observed when compared to the non-exposed plants. In tea - plants in water - it was also possible to quantify the phenolic compounds and it was observed that in the group of plants of the first 30 days there was a decrease in caffeic acid and an increase in coumaric and ferulic acids, compared to the group of plants that were not exposed to 2,4-D. In the remaining 30 days with the new seedlings there was a decrease of the coumaric acid and an increase of the caffeic and ferulic acids.