RESUMO
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.
Assuntos
Drosophila melanogaster/embriologia , Hipercinese/fisiopatologia , Sobrecarga de Ferro/embriologia , Animais , Comportamento Animal/fisiologia , Aminas Biogênicas/metabolismo , Aminas Biogênicas/fisiologia , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Feminino , Expressão Gênica/genética , Regulação da Expressão Gênica no Desenvolvimento/genética , Hipercinese/etiologia , Ferro/metabolismo , Ferro/fisiologia , Ferro/toxicidade , Sobrecarga de Ferro/metabolismo , Sobrecarga de Ferro/fisiopatologia , Locomoção/efeitos dos fármacos , Masculino , Exposição Materna , Atividade Motora/efeitos dos fármacos , Oxirredução , Exposição PaternaRESUMO
The behavior and neuronal ganglia integrity of Drosophila melanogaster larvae exposed to Bisphenol F (BPF) and Bisphenol S (BPS) (0.25, 0.5 and 1 mM) was evaluated. Larvae exposed to BPF and BPS (0.5 and 1 mM) showed hyperactivity, reduced decision-making capacity and were not responsive to touch (no sensitivity to physical stimuli). There was also a reduction in the tunneling capacity induced by 1 mM of BPF and BPS (innate behaviors for survival). Behaviors resulting from changes in neuronal functioning, thermotaxis and phototaxis showed that BPS was more harmful compared to BPF. Furthermore, the concentration of 1 mM BPS generated greater damage to neuronal ganglia when compared to BPF. This difference may be related to the LC50 of the 10.04 mM BPS and 15.07 mM BPF. However, these behavioral changes presented by the larvae here are characteristic of those presented in neurodevelopmental disorders. Our findings are novel and refute the possibility that BPF and BPS are safer alternatives.
Assuntos
Drosophila melanogaster , Fenóis , Animais , Larva , Fenóis/farmacologia , Compostos Benzidrílicos/toxicidadeRESUMO
Camu-camu (Myrciaria dubia) is known for its antioxidant properties, although little is known about its developmental safety effects, particularly on adult neural function under basal redox and oxidative stress conditions. Therefore, this study sought to address this gap by conducting three complementary protocols using Drosophila melanogaster to investigate these effects. The initial assays revealed that second-stage larvae consumed diets supplemented with various concentrations of camu-camu uniformly, establishing a 50% lethal concentration at 4.799 mg/mL. Hence, non-lethal (0.1, 0.5, and 1 mg/mL) and sub-lethal (5 and 10 mg/mL) concentrations were then chosen to evaluate the effects of camu-camu on preimaginal development and adult neural function. Our observations showed that camu-camu impacts the expression of antioxidant enzymes, reactive species, and lipoperoxidation. Notably, sub-lethal concentrations decreased preimaginal viability and locomotor activity, negatively influenced geotaxis and acetylcholinesterase activity, and increased reactive species, catalase, and glutathione S-transferase activity in flies. Additionally, the protective effects of camu-camu against oxidative stress induced by iron (20 mM) were assessed. Flies supplemented with 0.5 mg/mL of camu-camu during the larval period showed improved neural viability and function, and this supplementation was found to protect against oxidative stress. These findings are instrumental in evaluating the safety and efficacy of commercial supplements based on camu-camu, offering significant insights for future research and application.
RESUMO
Bisphenol F (BPF) and Bisphenol S (BPS) are being widely used by the industry with the claim of "safer substances", even with the scarcity of toxicological studies. Given the etiological gap of autism spectrum disorder (ASD), the environment may be a causal factor, so we investigated whether exposure to BPF and BPS during the developmental period can induce ASD-like modeling in adult flies. Drosophila melanogaster flies were exposed during development (embryonic and larval period) to concentrations of 0.25, 0.5, and 1 mM of BPF and BPS, separately inserted into the food. When they transformed into pupae were transferred to a standard diet, ensuring that the flies (adult stage) did not have contact with bisphenols. Thus, after hatching, consolidated behavioral tests were carried out for studies with ASD-type models in flies. It was observed that 1 mM BPF and BPS caused hyperactivity (evidenced by open-field test, negative geotaxis, increased aggressiveness and reproduction of repetitive behaviors). The flies belonging to the 1 mM groups of BPF and BPS also showed reduced cognitive capacity, elucidated by the learning behavior through aversive stimulus. Within the population dynamics that flies exposed to 1 mM BPF and 0.5 and 1 mM BPS showed a change in social interaction, remaining more distant from each other. Exposure to 1 mM BPF, 0.5 and 1 mM BPS increased brain size and reduced Shank immunoreactivity of adult flies. These findings complement each other and show that exposure to BPF and BPS during the development period can elucidate a model with endophenotypes similar to ASD in adult flies. Furthermore, when analyzing comparatively, BPS demonstrated a greater potential for damage when compared to BPF. Therefore, in general these data sets contradict the idea that these substances can be used freely.
Assuntos
Compostos Benzidrílicos , Drosophila melanogaster , Endofenótipos , Fenóis , Sulfonas , Animais , Drosophila melanogaster/efeitos dos fármacos , Fenóis/toxicidade , Sulfonas/toxicidade , Compostos Benzidrílicos/toxicidade , Comportamento Animal/efeitos dos fármacos , Modelos Animais de Doenças , Larva/efeitos dos fármacos , Masculino , Feminino , Transtorno do Espectro Autista/induzido quimicamenteRESUMO
Evidence has shown that consuming trans fatty acids (TFA) during development leads to their incorporation into the nervous tissue, resulting in neurological changes in flies. In this study, Drosophila melanogaster was exposed to different concentrations of hydrogenated vegetable fat (HVF) during development: substitute hydrogenated vegetable fat (SHVF), HVF 10 %, and HVF 20 %. The objective was to evaluate the effects of early trans fat exposure on cognition and associated pathways in flies. The results showed that early TFA exposure provoked a cerebral redox imbalance, as confirmed by increased reactive species (HVF 10 and 20 %) and lipid peroxidation (SHVF, HVF 10, and 20 %), reduced nuclear factor erythroid 2-related factor 2 immunoreactivity (HVF 10 and 20 %), and increased heat shock protein 70 (HVF 20 %), which was possibly responsible for decreasing superoxide dismutase (SHVF, HVF 10, and 20 %) and catalase (HVF 20 %) activities. Furthermore, the presence of TFA in nervous tissue impaired learning (HVF 10 and 20 %) and memory at 6 and 24 h (SHVF, HVF 10, and 20 %). These cognitive impairments may be linked to reduced Shank levels (HVF 20 %) and increased acetylcholinesterase activity (SHVF, HVF 10 and 20 %) observed. Our findings demonstrate that early exposure to trans fat leads to cerebral redox imbalance, altering proteins associated with stress, synaptic plasticity, and the cholinergic system, consequently leading to cognitive impairment in flies.
Assuntos
Disfunção Cognitiva , Ácidos Graxos trans , Animais , Drosophila melanogaster , Ácidos Graxos trans/toxicidade , Acetilcolinesterase , Estresse Oxidativo , Disfunção Cognitiva/induzido quimicamente , Plasticidade NeuronalRESUMO
Neurodevelopmental disorders, such as autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD), are characterized by persistent changes in communication and social interaction, as well as restricted and stereotyped patterns of behavior. The complex etiology of these disorders possibly combines the effects of multiple genes and environmental factors. Hence, exposure to insecticides such as imidacloprid (IMI) has been used to replicate the changes observed in these disorders. Lutein is known for its anti-inflammatory and antioxidant properties and is associated with neuroprotective effects. Therefore, the aim of this study was to evaluate the protective effect of lutein-loaded nanoparticles, along with their mechanisms of action, on Drosophila melanogaster offspring exposed to IMI-induced damage. To simulate the neurodevelopmental disorder model, flies were exposed to a diet containing IMI for 7â¯days. Posteriorly, their offspring were exposed to a diet containing lutein-loaded nanoparticles for a period of 24â¯h, and male and female flies were subjected to behavioral and biochemical evaluations. Treatment with lutein-loaded nanoparticles reversed the parameters of hyperactivity, aggressiveness, social interaction, repetitive movements, and anxiety in the offspring of flies exposed to IMI. It also protected markers of oxidative stress and cell viability, in addition to preventing the reduction of Nrf2 and Shank3 immunoreactivity. These results demonstrate that the damage induced by exposure to IMI was restored through treatment with lutein-loaded nanoparticles, elucidating lutein's mechanisms of action as a therapeutic agent, which, after further studies, can become a co-adjuvant in the treatment of neurodevelopmental disorders, such as ASD and ADHD.
RESUMO
Bisphenol F (BPF) and Bisphenol S (BPS) are safe alternatives substances? Here Drosophila melanogaster were exposed during development (larval stage) to BPF and BPS (0.25, 0.5 and 1 mM). Upon reaching the last larval stage (3rd stage), markers of oxidative stress and metabolism of both substances were evaluated, along with investigation of mitochondrial and cell viability. This study is attributed to an unprecedented fact: BPF and BPS exposed larvae, both at concentrations of 0.5 and 1 mM, showed higher cytochrome P-450 (CYP450) activity. The GST activity increased in all BPF and BPS concentrations, and reactive species, lipid peroxidation, superoxide dismutase, and catalase activity increased in larvae (BPF and BPS; 0.5, and 1 mM); nonetheless, mitochondrial and cell viability decreased with 1 mM of BPF and BPS. In addition, the reduced number of pupae formed in the 1 mM BPF and BPS groups and melanotic mass formation may be attributed to oxidative stress. From the pupae formed, the hatching rate reduced in the 0.5 and 1 mM BPF and BPS groups. Thus, the possible presence of toxic metabolites may be related to the larval oxidative stress condition, which is detrimental to the complete development of Drosophila melanogaster.
Assuntos
Drosophila melanogaster , Estresse Oxidativo , Animais , Fenóis/toxicidade , Compostos Benzidrílicos/toxicidadeRESUMO
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.
Assuntos
Nanopartículas , Fármacos Neuroprotetores , Doença de Parkinson , Animais , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/prevenção & controle , Drosophila melanogaster , beta Caroteno/farmacologia , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Dopamina , Rotenona , Espécies Reativas de Oxigênio , Fármacos Neuroprotetores/farmacologia , Substâncias Reativas com Ácido Tiobarbitúrico , Acetilcolinesterase/metabolismo , Estresse Oxidativo , Superóxido Dismutase/metabolismo , Modelos Animais de DoençasRESUMO
We investigated a possible toxic effect induced by chronic exposure to free curcumin and curcumin-loaded nanocapsules in Drosophila melanogaster, enabling safe applications. Flies of both sexes were divided into groups: control group; free curcumin at concentrations of 10, 30, 100, 300, 900, and 3000 µM; curcumin-loaded nanocapsules at concentrations of 10, 30, 100, and 300 µM. Initially, the diet consumption test was evaluated in flies exposed to different concentrations. During the 10-day treatment, the flies were evaluated for percentage survival. After the treatment, behaviors (geotaxis negative and open field), acetylcholinesterase activity (AChE), and oxidative stress parameters (reactive species (RS) and thiobarbituric acid reactive substances (TBARS) levels, Glutathione-S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT) enzymes activity, erythroid-derived nuclear factor 2 (Nrf2) immunoreactivity, and cellular metabolic capacity, were assessed. No significant difference in diet consumption, indicating that the flies equally consumed the different concentrations of free curcumin and the curcumin-loaded nanocapsules. Was observed that free curcumin and curcumin-loaded nanocapsules increased survival, locomotor and exploratory performance, decreased AChE activity, RS and TBARS levels, increased GST, SOD and CAT activity, Nrf2 and viable cells compared to the control. The chronic treatment did not cause toxicity, suggesting that nanoencapsulation of curcumin could be explored.
Assuntos
Curcumina , Nanocápsulas , Animais , Masculino , Feminino , Drosophila melanogaster , Curcumina/toxicidade , Nanocápsulas/toxicidade , Acetilcolinesterase/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico , Estresse Oxidativo , Antioxidantes/farmacologia , Superóxido Dismutase/metabolismo , Catalase/metabolismoRESUMO
Female and male Drosophila melanogaster were exposed separately for seven days to Bisphenol A (BPA), Bisphenol F (BPF), and Bisphenol S (BPS) at concentrations of 0.25, 0.5, and 1 mM. We observed that males exposed to 0.5 and 1 mM BPS showed lower catalase (CAT) activity and higher superoxide dismutase (SOD) and reactive species (RS); CAT activity decreased for BPF 0.5 and 1 mM. Nevertheless, BPA 0.5 and 1 mM decreased CAT activity, increased RS and lipid peroxidation (LPO), and reduced mitochondrial viability. None of the bisphenols altered the cell viability of male flies, although BPA 0.5 and 1 mM reduced longevity. In female flies, BPA and BPS 0.5 and 1 mM increased RS and LPO levels and decreased CAT activity and glutathione-S-transferase (GST), which may have contributed to lower mitochondrial and cell viability. Furthermore, BPS decreased SOD activity at the 1 mM concentration, and BPA reduced the SOD activity at concentrations of 0.5 and 1 mM. In the BPF 1 mM group, there was a reduction in GST activity and an increase in RS and LPO levels. The toxicological effects were different between sexes, and BPA was more harmful than BPF and BPS in male flies. Thus, our findings showed that females were more susceptible to oxidative cell damage when exposed to BPA and BPS than to BPF, and daily exposure to BPA and BPS at all concentrations reduced female longevity, as well as in BPF 1 mM.
Assuntos
Drosophila melanogaster , Longevidade , Animais , Antioxidantes , Compostos Benzidrílicos/toxicidade , Drosophila melanogaster/metabolismo , Feminino , Glutationa Transferase , Masculino , Estresse Oxidativo , Fenóis , Superóxido Dismutase/metabolismoRESUMO
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.
Assuntos
Hesperidina , Doença de Parkinson , Animais , Modelos Animais de Doenças , Dopamina , Drosophila melanogaster , Hesperidina/farmacologia , Hesperidina/uso terapêutico , Levodopa , Doença de Parkinson/tratamento farmacológicoRESUMO
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.
Assuntos
Comportamento Animal/efeitos dos fármacos , Compostos Benzidrílicos/toxicidade , Dopamina/metabolismo , Drosophila melanogaster/efeitos dos fármacos , Fenóis/toxicidade , Animais , Catalase/metabolismo , Dopamina/fisiologia , Drosophila melanogaster/embriologia , Drosophila melanogaster/crescimento & desenvolvimento , Feminino , Fertilidade/efeitos dos fármacos , Glutationa Transferase/metabolismo , Masculino , Teste de Campo Aberto/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Pupa/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Tirosina/metabolismo , Tirosina 3-Mono-Oxigenase/efeitos dos fármacos , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
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.