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1.
bioRxiv ; 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38915533

RESUMO

The brain exhibits remarkable neuronal diversity which is critical for its functional integrity. From the sheer number of cell types emerging from extensive transcriptional, morphological, and connectome datasets, the question arises of how the brain is capable of generating so many unique identities. 'Terminal selectors' are transcription factors hypothesized to determine the final identity characteristics in post-mitotic cells. Which transcription factors function as terminal selectors and the level of control they exert over different terminal characteristics are not well defined. Here, we establish a novel role for the transcription factor broad as a terminal selector in Drosophila melanogaster. We capitalize on existing large sequencing and connectomics datasets and employ a comprehensive characterization of terminal characteristics including Perturb-seq and whole-cell electrophysiology. We find a single isoform broad-z4 serves as the switch between the identity of two visual projection neurons LPLC1 and LPLC2. Broad-z4 is natively expressed in LPLC1, and is capable of transforming the transcriptome, morphology, and functional connectivity of LPLC2 cells into LPLC1 cells when perturbed. Our comprehensive work establishes a single isoform as the smallest unit underlying an identity switch, which may serve as a conserved strategy replicated across developmental programs.

2.
Elife ; 122024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38634460

RESUMO

Mechanosensory neurons located across the body surface respond to tactile stimuli and elicit diverse behavioral responses, from relatively simple stimulus location-aimed movements to complex movement sequences. How mechanosensory neurons and their postsynaptic circuits influence such diverse behaviors remains unclear. We previously discovered that Drosophila perform a body location-prioritized grooming sequence when mechanosensory neurons at different locations on the head and body are simultaneously stimulated by dust (Hampel et al., 2017; Seeds et al., 2014). Here, we identify nearly all mechanosensory neurons on the Drosophila head that individually elicit aimed grooming of specific head locations, while collectively eliciting a whole head grooming sequence. Different tracing methods were used to reconstruct the projections of these neurons from different locations on the head to their distinct arborizations in the brain. This provides the first synaptic resolution somatotopic map of a head, and defines the parallel-projecting mechanosensory pathways that elicit head grooming.


Assuntos
Drosophila , Neurônios , Animais , Asseio Animal/fisiologia , Vias Aferentes , Neurônios/fisiologia , Encéfalo , Drosophila melanogaster/fisiologia
3.
J Toxicol Environ Health A ; 87(12): 497-515, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38619158

RESUMO

One prominent aspect of Parkinson's disease (PD) is the presence of elevated levels of free radicals, including reactive oxygen species (ROS). Syagrus coronata (S. coronata), a palm tree, exhibits antioxidant activity attributed to its phytochemical composition, containing fatty acids, polyphenols, and flavonoids. The aim of this investigation was to examine the potential neuroprotective effects of S. coronata fixed oil against rotenone-induced toxicity using Drosophila melanogaster. Young Drosophila specimens (3-4 d old) were exposed to a diet supplemented with rotenone (50 µM) for 7 d with and without the inclusion of S. coronata fixed oil (0.2 mg/g diet). Data demonstrated that rotenone exposure resulted in significant locomotor impairment and increased mortality rates in flies. Further, rotenone administration reduced total thiol levels but elevated lipid peroxidation, iron (Fe) levels, and nitric oxide (NO) levels while decreasing the reduced capacity of mitochondria. Concomitant administration of S. coronata exhibited a protective effect against rotenone, as evidenced by a return to control levels of Fe, NO, and total thiols, lowered lipid peroxidation levels, reversed locomotor impairment, and enhanced % cell viability. Molecular docking of the oil lipidic components with antioxidant enzymes showed strong binding affinity to superoxide dismutase (SOD) and glutathione peroxidase (GPX1) enzymes. Overall, treatment with S. coronata fixed oil was found to prevent rotenone-induced movement disorders and oxidative stress in Drosophila melanogaster.


Assuntos
Transtornos dos Movimentos , Rotenona , Animais , Drosophila melanogaster , Simulação de Acoplamento Molecular , Estresse Oxidativo , Antioxidantes/farmacologia , Óxido Nítrico/metabolismo
4.
J Mycol Med ; 34(2): 101475, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38479291

RESUMO

Malassezia pachydermatis is often reported as the causative agent of dermatitis in dogs. This study aims to evaluate the in vitro and in vivo antifungal activity of azoles and terbinafine (TRB), alone and in combination with the 8-hydroxyquinoline derivatives (8-HQs) clioquinol (CQL), 8-hydroxyquinoline-5-(n-4-chlorophenyl)sulfonamide (PH151), and 8-hydroxyquinoline-5-(n-4-methoxyphenyl)sulfonamide (PH153), against 16 M. pachydermatis isolates. Susceptibility to the drugs was evaluated by in vitro broth microdilution and time-kill assays. The Toll-deficient Drosophila melanogaster fly model was used to assess the efficacy of drugs in vivo. In vitro tests showed that ketoconazole (KTZ) was the most active drug, followed by TRB and CQL. The combinations itraconazole (ITZ)+CQL and ITZ+PH151 resulted in the highest percentages of synergism and none of the combinations resulted in antagonism. TRB showed the highest survival rates after seven days of treatment of the flies, followed by CQL and ITZ, whereas the evaluation of fungal burden of dead flies showed a greater fungicidal effect of azoles when compared to the other drugs. Here we showed for the first time that CQL is effective against M. pachydermatis and potentially interesting for the treatment of malasseziosis.


Assuntos
Antifúngicos , Azóis , Dermatomicoses , Drosophila melanogaster , Malassezia , Testes de Sensibilidade Microbiana , Animais , Antifúngicos/farmacologia , Malassezia/efeitos dos fármacos , Malassezia/crescimento & desenvolvimento , Azóis/farmacologia , Dermatomicoses/tratamento farmacológico , Dermatomicoses/microbiologia , Drosophila melanogaster/microbiologia , Drosophila melanogaster/efeitos dos fármacos , Cães , Terbinafina/farmacologia , Sinergismo Farmacológico , Quimioterapia Combinada , Doenças do Cão/microbiologia , Doenças do Cão/tratamento farmacológico , Cetoconazol/farmacologia , Oxiquinolina/farmacologia , Sulfonamidas/farmacologia , Itraconazol/farmacologia , Clioquinol/farmacologia , Modelos Animais de Doenças
5.
Neurotoxicol Teratol ; 103: 107348, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38554851

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 quimicamente
6.
Odontology ; 112(4): 1178-1185, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38493437

RESUMO

The aim of this work was to evaluate the toxicological action of AH Plus (AHP), Bio-C Sealer (BCS), and EndoSequence BC Sealer (ESB), using Drosophila melanogaster as the model organism performing in vivo and ex vivo analysis. D. melanogaster were exposed for 10 days to three concentrations (5 mg/ml, 10 mg/ml, and 20 mg/ml) of AHP, BCS, and ESB sealers mixed with 10 ml of standard diet. During this period, the mortality of flies was evaluated. On the 11th day, the locomotor activity test was performed and the flies were euthanized for oxidative damage analysis (reactive species and lipid peroxidation) and cell viability (resazurin reduction). For the mortality curves evaluation, the log-rank test (Mantel-Cox) was used. For the analysis of other data, a one-way analysis of variance (ANOVA) was applied, followed by Tukey's post hoc test (α = 0.05). Regarding mortality, there were no significant differences. The locomotor activity was reduced, mainly in the two highest concentrations of AHP and BCS. Besides, reactive species generation was bigger in the AHP 20 mg/ml group. AHP induced a lipid peroxidation increase in all three concentrations tested, when compared to other sealers. Considering cell viability, the two highest concentrations of AHP reduced this parameter; while in other sealers, viability was reduced only in the highest concentration. AHP showed changes in oxidative markers that led to greater damage to the flies.


Assuntos
Sobrevivência Celular , Drosophila melanogaster , Peroxidação de Lipídeos , Estresse Oxidativo , Materiais Restauradores do Canal Radicular , Animais , Drosophila melanogaster/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Materiais Restauradores do Canal Radicular/toxicidade , Peroxidação de Lipídeos/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Resinas Epóxi/toxicidade , Teste de Materiais
7.
Antioxidants (Basel) ; 13(1)2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38247526

RESUMO

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.

8.
Behav Brain Res ; 459: 114753, 2024 02 29.
Artigo em Inglês | MEDLINE | ID: mdl-37949320

RESUMO

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/toxicidade
9.
Mol Neurobiol ; 61(3): 1225-1236, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37698834

RESUMO

Type 2 diabetes mellitus (T2DM) has been shown to affect a series of cognitive processes including memory, increasing the risk for dementia, particularly Alzheimer's disease (AD). Although increasing evidence has supported that both diseases share common features, the pathophysiological mechanisms connecting these two disorders remain to be fully elucidated. Herein, we used Drosophila melanogaster fed on a high-sugar diet (HSD) to mimic T2DM, and investigate its effects on memory as well as identify potential molecular players associated with the memory deficits induced by HSD. Flies hatched from and reared on HSD for 7 days had a substantial decrease in short-term memory (STM). The screening for memory-related genes using transcriptome data revealed that HSD altered the expression of 33% of memory genes in relation to the control. Among the differentially expressed genes (DEGs) with a fold change (FC) higher than two, we found five genes, related to synapse and memory trace formation, that could be considered strong candidates to underlie the STM deficits in HSD flies: Abl tyrosine kinase (Abl), bruchpilot (Brp), minibrain (Mnb), shaker (Sh), and gilgamesh (Gish). We also analyzed genes from the dopamine system, one of the most relevant signaling pathways for olfactory memory. Interestingly, the flies fed on HSD presented a decreased expression of the Tyrosine hydroxylase (Ple) and Dopa decarboxylase (Ddc) genes, signals of a possible dopamine deficiency. In this work, we present promising biomarkers to investigate molecular networks shared between T2DM and AD.


Assuntos
Doença de Alzheimer , Diabetes Mellitus Tipo 2 , Animais , Drosophila melanogaster/metabolismo , Dopamina/metabolismo , Transtornos da Memória/genética , Dieta , Açúcares/metabolismo , Açúcares/farmacologia
10.
J Comp Physiol B ; 193(5): 479-493, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37500966

RESUMO

This study investigated the potential effects of exercise on the responses of energy metabolism, redox balance maintenance, and apoptosis regulation in Drosophila melanogaster to shed more light on the mechanisms underlying the increased performance that this emerging exercise model provides. Three groups were evaluated for seven days: the control (no exercise or locomotor limitations), movement-limited flies (MLF) (no exercise, with locomotor limitations), and EXE (with exercise, no locomotor limitations). The EXE flies demonstrated greater endurance-like tolerance in the swimming test, associated with increased citrate synthase activity, lactate dehydrogenase activity and lactate levels, and metabolic markers in exercise. Notably, the EXE protocol regulated the Akt/p38 MAPK/Nrf2 pathway, which was associated with decreased Hsp70 activation, culminating in glutathione turnover regulation. Moreover, reducing the locomotion environment in the MLF group decreased endurance-like tolerance and did not alter citrate synthase activity, lactate dehydrogenase activity, or lactate levels. The MLF treatment promoted a pro-oxidant effect, altering the Akt/p38 MAPK/Nrf2 pathway and increasing Hsp70 levels, leading to a poorly-regulated glutathione system. Lastly, we demonstrated that exercise could modulate major metabolic responses in Drosophila melanogaster aerobic and anaerobic metabolism, associated with apoptosis and cellular redox balance maintenance in an emergent exercise model.


Assuntos
Drosophila melanogaster , Proteínas Quinases p38 Ativadas por Mitógeno , Animais , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Drosophila melanogaster/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Citrato (si)-Sintase/metabolismo , Oxirredução , Glutationa/metabolismo , Lactato Desidrogenases/metabolismo , Lactatos
11.
Arch Toxicol ; 97(9): 2329-2342, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37394624

RESUMO

Cell culture and invertebrate animal models reflect a significant evolution in scientific research by providing reliable evidence on the physiopathology of diseases, screening for new drugs, and toxicological tests while reducing the need for mammals. In this review, we discuss the progress and promise of alternative animal and non-animal methods in biomedical research, with a special focus on drug toxicity.


Assuntos
Pesquisa Biomédica , Animais , Modelos Animais , Mamíferos
12.
Mycoses ; 66(10): 906-910, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37434424

RESUMO

BACKGROUND: Dermatophytosis is one of the most common fungal infections worldwide. The distribution of dermatophytes varies across continents, but the genera Trichophyton and Microsporum have emerged as the main isolated agents in humans and animals. OBJECTIVES: To validate Drosophila melanogaster flies as a fast and feasible model to study dermatophytic infections. METHODS: Wild-type (WT) and Toll-deficient D. melanogaster flies were infected by Trichophyton rubrum, T. mentagrophytes, Microsporum canis and Nannizzia gypsea by pricking with a needle previously dipped in inoculum concentrations ranging from 103 to 108 colony-forming units/mL. Establishment of infection was confirmed by survival curves, histopathological analysis and fungal burden. Thereafter, flies were treated with terbinafine, itraconazole and clioquinol. RESULTS: WT flies were predominantly resistant to the infection, whereas Toll-deficient flies succumbed to the four dermatophyte genera tested. The antifungal drugs protected flies from the infection, except for N. gypsea whose survival curves did not differ from the untreated group. CONCLUSIONS: This pilot study confirms that D. melanogaster is a suitable model to study the virulence and antifungal drug efficacy in dermatophyte species.


Assuntos
Arthrodermataceae , Tinha , Humanos , Animais , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Drosophila melanogaster , Projetos Piloto , Itraconazol , Trichophyton , Tinha/tratamento farmacológico , Tinha/microbiologia
13.
Int J Mol Sci ; 24(12)2023 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-37373426

RESUMO

One of the largest health problems worldwide is the development of chronic noncommunicable diseases due to the consumption of hypercaloric diets. Among the most common alterations are cardiovascular diseases, and a high correlation between overnutrition and neurodegenerative diseases has also been found. The urgency in the study of specific damage to tissues such as the brain and intestine led us to use Drosophila melanogaster to study the metabolic effects caused by the consumption of fructose and palmitic acid in specific tissues. Thus, third instar larvae (96 ± 4 h) of the wild Canton-S strain of D. melanogaster were used to perform transcriptomic profiling in brain and midgut tissues to test for the potential metabolic effects of a diet supplemented with fructose and palmitic acid. Our data infer that this diet can alter the biosynthesis of proteins at the mRNA level that participate in the synthesis of amino acids, as well as fundamental enzymes for the dopaminergic and GABAergic systems in the midgut and brain. These also demonstrated alterations in the tissues of flies that may help explain the development of various reported human diseases associated with the consumption of fructose and palmitic acid in humans. These studies will not only help to better understand the mechanisms by which the consumption of these alimentary products is related to the development of neuronal diseases but may also contribute to the prevention of these conditions.


Assuntos
Drosophila melanogaster , Doenças Neurodegenerativas , Animais , Humanos , Drosophila melanogaster/metabolismo , Frutose/metabolismo , Ácido Palmítico/farmacologia , Larva/metabolismo , Doenças Neurodegenerativas/genética , Expressão Gênica
14.
Toxins (Basel) ; 15(6)2023 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-37368659

RESUMO

Zearalenone (ZEN) is a non-steroidal mycoestrogen produced by the Fusarium genus. ZEN and its metabolites compete with 17-beta estradiol for cytosolic estrogen receptors, causing reproductive alterations in vertebrates. ZEN has also been associated with toxic and genotoxic effects, as well as an increased risk for endometrial adenocarcinomas or hyperplasia, breast cancer, and oxidative damage, although the underlying mechanisms remain unclear. Previous studies have monitored cellular processes through levels of transcripts associated with Phase I Xenobiotic Metabolism (Cyp6g1 and Cyp6a2), oxidative stress (hsp60 and hsp70), apoptosis (hid, grim, and reaper), and DNA damage genes (Dmp53). In this study, we evaluated the survival and genotoxicity of ZEN, as well as its effects on emergence rate and fecundity in Drosophila melanogaster. Additionally, we determined levels of reactive oxygen species (ROS) using the D. melanogaster flare and Oregon R(R)-flare strains, which differ in levels of Cyp450 gene expression. Our results showed that ZEN toxicity did not increase mortality by more than 30%. We tested three ZEN concentrations (100, 200, and 400 µM) and found that none of the concentrations were genotoxic but were cytotoxic. Taking into account that it has previously been demonstrated that ZEN administration increased hsp60 expression levels and apoptosis gene transcripts in both strains, the data agree with an increase in ROS and development and fecundity alterations. Since Drosophila lacks homologous genes for mammalian estrogen receptors alpha and beta, the effects of this mycotoxin can be explained by a mechanism different from estrogenic activity.


Assuntos
Zearalenona , Animais , Zearalenona/metabolismo , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Estresse Oxidativo , Dano ao DNA , Fertilidade , Mamíferos/metabolismo
15.
J Biochem Mol Toxicol ; 37(7): e23356, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37009961

RESUMO

Zidovudine (AZT) is the most commonly prescribed antiviral drug for the treatment of human immunodeficiency virus (HIV) infection. However, its chronic administration causes toxic side effects limiting its use. This study aimed to evaluate the toxicity of different concentrations of AZT and novel chalcogen derivatives (7A, 7D, 7G, 7K, 7M) on locomotion, mitochondrial dysfunction, acetylcholinesterase (AChE) activity, and production of reactive oxygen species (ROS) in adult Drosophila melanogaster. Our results show that AZT and its derivative 7K at a concentration of 10 µM impaired flies' locomotor behavior. Furthermore, AZT and the derivatives 7K, 7A, and 7M induced mitochondrial dysfunction observed by a decrease in oxygen flux through mitochondrial complexes I and II. Neither of the compounds tested affected AChE activity or ROS production in flies. According to these data, AZT derivatives presented the following decreasing order of toxicity: 7K > AZT > 7G > 7A > 7M > 7D. Based on the chemical structure, it is possible to infer that the presence of the seleno-phenyl group in 7A and 7G increases their toxicity compared to compounds 7D and 7M. In addition, compounds 7G, 7M, and 7K with three carbon atoms as spacer were more toxic than analogs containing one carbon atom (7A and 7D). Finally, the insertion of a p-methoxyl group enhances toxicity (7K). Based on these results, excepting 7K, all other chalcogen derivatives presented lower toxicity than AZT and are potential drug candidates.


Assuntos
Fármacos Anti-HIV , Calcogênios , Animais , Humanos , Zidovudina/toxicidade , Drosophila melanogaster , Espécies Reativas de Oxigênio , Acetilcolinesterase , Fármacos Anti-HIV/toxicidade
16.
Food Chem Toxicol ; 175: 113701, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36863561

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/toxicidade
17.
Gen Comp Endocrinol ; 335: 114229, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-36781022

RESUMO

The insulin pathway is a crucial central system for metabolism and growth. The Nrf2 signaling pathway functions to counteract oxidative stress. Here we sought to study the consequences of an oxidative stress challenge to insulin compromised and control adult flies of different ages, varying the activation state of the Nrf2 pathway in flies, the Cap'n'collar C pathway. For this, we employed two different pro-oxidative conditions: 3 % hydrogen peroxide or 20 mM paraquat laced in the food. In both cases, wild type (control) flies die within a few days, yet there are significant differences between males and females, and also within flies of different ages (seven versus thirty days old flies). We repeated the same conditions with young (seven days old) flies that were heterozygous for a loss-of-function mutation in Keap1. There were no significant differences. We then tested two hypomorphic viable conditions of the insulin pathway (heteroallelic combination for the insulin receptor and the S6 Kinase), challenged in the same way: Whereas they also die in the pro-oxidant conditions, they fare significantly better when heterozygous for Keap1, in contrast to controls. We also monitored locomotion in all of these conditions, and, in general, found significant differences between flies without and with a mutant allele (heterozygous) for Keap1. Our results point to altered oxidative stress conditions in diabetic flies. These findings suggest that modest activation of the Cap'n'collar C pathway may be a treatment for diabetic symptoms.


Assuntos
Diabetes Mellitus , Insulinas , Animais , Masculino , Feminino , Drosophila/genética , Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Estresse Oxidativo/fisiologia , Vertebrados/metabolismo , Transdução de Sinais/fisiologia , Insulinas/metabolismo
18.
Sci Total Environ ; 873: 162150, 2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-36773916

RESUMO

The demand for food to feed the growing world population has been promoting the indiscriminate use of chemical fertilizers, which can be detrimental to the environment. In order to maintain high crop productivity without damaging the ecosystem, biofertilizers have emerged as alternative to reduce the use of chemical fertilizers. So, environmentally safer biofertilizer can replace the exploitation of more toxic chemical fertilizer. Here, the fly Drosophila melanogaster was used to study the potential toxicity of the biofertilizer Beifort®. Flies were exposed to high concentrations of Beifort® in the diet (1.8 mL/L, 9.0 mL/L and 18 mL/L), and morphological and behavioral endpoints of toxicity were analyzed (development from egg to adult age, flies longevity, climbing performance, memory and learning of an associative learning, larvae digestive tract damage and plasmid DNA break). Beifort® did not modify flies development, survival, digestive track cell damage, locomotor activity or memory. Beifort® did not induce DNA breakage in vitro and had no toxicity to the non-target D. melanogaster after in vivo exposure. Thus, in addition of promoting the sustainable use of agricultural wastes, the exploitation of Beifort® can contribute to decrease the use of chemical fertilizers.


Assuntos
Drosophila melanogaster , Ecossistema , Animais , Fertilizantes/toxicidade , Fertilizantes/análise , Agricultura , Produção Agrícola
19.
J Am Nutr Assoc ; 42(3): 285-294, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35512766

RESUMO

OBJECTIVE: The metabolic effects of chronic consumption of food laced with different doses of moringa leaf powder (MLP) were assessed using a heteroallelic mutant of the sole insulin receptor gene of Drosophila melanogaster (InR), and the yellow,white (y,w) control stock. METHODS: The MLP composition was partially determined. Both strains were raised in a standard diet (SD) or in a SD supplemented with different MLP doses (0.5, 1.5, 2.5, 4.0, and 5.5%) until 4-5 days of emergence. Afterward, the total carbohydrate, lipid, glucose, and triacylglyceride levels were measured in the flies. Additionally, survival and weight changes were reported. For metabolic tests, female and male virgin flies were evaluated separately. RESULTS: Low MLP supplementation improved carbohydrate and glucose levels in the y,w strain. Additionally, the InR-mutant strain reported lower lipid content when subjected to the same regimes. Survival improved in both strains with low MLP doses, while chronic consumption of high MLP doses resulted in triacylglycerides increase, weight gain, and survival reduction. CONCLUSION: Low doses of MLP supplementation improves some metabolic parameters that affect flies' survival, especially in the y,w strain. Furthermore, the same low doses of MLP treatments also resulted in metabolic improvements in the InR-mutant flies; however, MLP consumption levels should be carefully assessed.Supplemental data for this article is available online at.


Assuntos
Diabetes Mellitus Tipo 2 , Moringa oleifera , Moringa , Masculino , Feminino , Animais , Drosophila melanogaster , Pós , Glucose , Folhas de Planta , Lipídeos
20.
Arch Insect Biochem Physiol ; 112(4): e21994, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36567513

RESUMO

In this study, we have demonstrated, for the first time, the muscular protective effects of Piranhea trifoliata bark extract against Paraquat (PQ)-induced oxidative stress in Drosophila melanogaster. Exposure of D. melanogaster (Canton Special) to PQ caused oxidative stress, as evidenced by protein carbonyl and elevated acetylcholinesterase (AChE) activity levels. However, a diet supplemented with the P. trifoliata extracts (0.1 mg/ml) for 10 days ameliorates protein carbonyl levels and enzymatic activities of AChE and citrate synthase to prevent PQ damage. Also, P. trifoliata bark extracts showed in phytochemical assays the presence of phenols, at 46.06 mg EAG/g extract of total phenolic compounds, and a 40% 2,2-diphenyl-1-picryl-hydrazyl scavenging effect. The study showed the muscular protective function of the P. trifoliata extracts in D. melanogaster exposed to PQ. On the basis of the results, we contemplate that the bark of P. trifoliata might prevent and ameliorate human diseases caused by oxidative stress. The muscular action of the P. trifoliata extract can be attributed to the antioxidant constituents, while the precise mechanism of its action needs further investigation.


Assuntos
Drosophila melanogaster , Paraquat , Animais , Humanos , Paraquat/toxicidade , Acetilcolinesterase/metabolismo , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Estresse Oxidativo , Extratos Vegetais/farmacologia , Extratos Vegetais/metabolismo , Fenóis/metabolismo , Fenóis/farmacologia
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