RESUMEN
The Chinese bayberry pomace wine (CPW) was prepared with the assisted fermentation of lactic acid bacteria and acetic acid bacteria, and its antioxidant effect on Drosophila melanogaster was researched. After mixed fermentation, CPW had a better color, which means there was more retention of anthocyanins, and the functional activity of anthocyanins could enhance the antioxidant capacity of flies. We found that the lifespan of flies exposed to CPW was prolonged, and the reproductive capacity of these flies was decreased. The food intake of flies was also influenced by CPW with gender differences. Furthermore, CPW alleviated the excessive proliferation of the intestinal precursor cells of H2O2-induced flies and activated the transcription level of antibacterial peptide genes. CPW had a protective effect on H2O2-induced acute injury flies, with an increased survival rate, enhanced SOD and CAT activities, and decreased malondialdehyde (MDA) content in flies. The expression of oxidative stress-related genes including CuZn-SOD, Mn-SOD, and CAT was also significantly upregulated by CPW, but the downregulation effect of CPW on age-related gene expression such as methuselah (MTH), the target of rapamycin (TOR) and ribosomaiprotein S6 kinase (S6K) was sex-specific. These results suggested that CPW played an important role in anti-oxidative stress injury, which was beneficial to promoting the reuse of by-products from Chinese bayberry processing.
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Antioxidantes , Drosophila melanogaster , Fermentación , Myrica , Estrés Oxidativo , Vino , Animales , Drosophila melanogaster/efectos de los fármacos , Drosophila melanogaster/metabolismo , Estrés Oxidativo/efectos de los fármacos , Vino/análisis , Antioxidantes/farmacología , Antioxidantes/metabolismo , Masculino , Femenino , Myrica/química , Longevidad/efectos de los fármacos , Antocianinas/farmacología , Peróxido de Hidrógeno/metabolismo , Frutas/química , Pueblos del Este de AsiaRESUMEN
Acrylamide (ACR) with its extensive industrial applications is a classified occupational hazard toxin and carcinogenic compound. Its formation in fried potatoes, red meat and coffee during high-temperature cooking is a cause for consideration. The fabrication of chitosan-coated probiotic nanoparticles (CSP NPs) aims to enhance the bioavailability of probiotics in the gut, thereby improving their efficacy against ACR-induced toxicity in Drosophila melanogaster. Nanoencapsulation, a vital domain of the medical nanotechnology field plays a key role in targeted drug delivery, bioavailability, multi-drug load delivery systems and synergistic treatment options. Our study exploited the nanoencapsulation technology to coat Lactobacillus fermentum (probiotic) with chitosan (prebiotic), both with substantial immunomodulatory effects, to ensure the stability and sustained release of microbial load and its secondary metabolites in the gut. The combination of pre-and probiotic components, called synbiotic formulations establishes the correlation between the gut microbiota and the overall well-being of an organism. Our study aimed to develop a potent synbiotic to alleviate the impacts of heat-processed dietary toxins that significantly influence behaviour, development, and survival. Our synbiotic co-treatment with ACR in fruit flies normalised neuro-behavioural, survival, redox status, and restored ovarian mitochondrial activity, contrasting with several physiological deficits observed in the ACR-treated model.
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Acrilamida , Quitosano , Drosophila melanogaster , Limosilactobacillus fermentum , Nanopartículas , Probióticos , Animales , Quitosano/química , Quitosano/farmacología , Probióticos/administración & dosificación , Nanopartículas/química , Acrilamida/química , Acrilamida/toxicidad , Drosophila melanogaster/efectos de los fármacos , Femenino , Microbioma Gastrointestinal/efectos de los fármacosRESUMEN
While much attention has been devoted to understanding the transcriptional changes underlying resistance to insecticides, comparatively little is known about the transcriptional response of naive insects to agrochemicals. In this study, we analyze the transcriptomic response of an insecticide susceptible strain of Drosophila melanogaster to nine agrochemicals using a robust method that goes beyond classical replication standards. Our findings demonstrate that exposure to piperonyl butoxide (PBO), but not to eight other compounds, elicits a robust transcriptional response in a wild-type strain of Drosophila melanogaster. PBO exposure leads to the upregulation of a subset of Cyps, GSTs, UGTs and EcKls. This response is both time and concentration-dependent, suggesting that the degree of inhibition of P450 activity correlates with the magnitude of the transcriptional response. Furthermore, the upregulation of these enzymes is excluded from reproductive organs. Additionally, different sets of genes are regulated in the digestive/secretory tract and the carcass. Our results suggest that P450s play a role in metabolizing yet unidentified endogenous compounds and are involved in an as-yet-unknown physiological regulatory feedback loop.
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Sistema Enzimático del Citocromo P-450 , Drosophila melanogaster , Butóxido de Piperonilo , Animales , Butóxido de Piperonilo/farmacología , Drosophila melanogaster/efectos de los fármacos , Drosophila melanogaster/genética , Sistema Enzimático del Citocromo P-450/genética , Sistema Enzimático del Citocromo P-450/metabolismo , Insecticidas/toxicidad , Insecticidas/farmacología , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Transcripción Genética/efectos de los fármacosRESUMEN
Enteropathy is a gastrointestinal disorder characterized by inflammation in the small intestine and one of the causes of enteropathy is the side effects of certain drugs, such as non-steroidal anti-inflammatory drugs (NSAIDs). The mechanism of NSAIDs, such as indomethacin, could inhibit prostaglandin synthesis, leading to a decrease in mucus production and small intestine integrity. To test the effects of a drug, it is necessary to undergo preclinical testing using animal models. Commonly used animal models such as mice and rats have several drawbacks including high cost, ethical issues, and long lifespan. Therefore, alternatives such as using invertebrate animals like Drosophila melanogaster as a more economical in vivo platform with genetic similarity to mammals and devoid of ethical concerns are needed. The aim of this study was to evaluate Drosophila melanogaster as an in vivo model organism in testing the side effects of pharmaceuticals that cause enteropathy. In this study, flies aged 3-5 days were starved and then placed into treatment vials comprising untreated control and indomethacin-treated (3.75 mM, 7.5 mM, and 15 mM). Survival analysis was conducted during the treatment period, followed by a Smurf assay test after seven days of treatment. Subsequently, the expression of pro-inflammatory cytokine-related genes (drs and totA), mitochondria stability-related genes (tom40), and endogenous antioxidant-related genes (sod1, sod2, and cat) was performed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Our data indicated that indomethacin did not impact lifespan or cause intestinal damage. However, we observed increased expression of pro-inflammatory cytokine-related genes, including drs, and a twofold increase in totA gene expression. Furthermore, there was a significant upregulation of mitochondrial stability gene tom40, endogenous antioxidant genes sod1 and cat, and a threefold increase in sod2 at 15 mM indomethacin. Although no phenotypical changes in gut integrity were detected, the increased expression of pro-inflammatory cytokine genes suggests the occurrence of inflammation in the indomethacin-treated flies.
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Antiinflamatorios no Esteroideos , Drosophila melanogaster , Indometacina , Enfermedades Intestinales , Animales , Drosophila melanogaster/efectos de los fármacos , Indometacina/efectos adversos , Indometacina/farmacología , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/efectos adversos , Enfermedades Intestinales/inducido químicamente , Enfermedades Intestinales/patología , Enfermedades Intestinales/genética , Enfermedades Intestinales/tratamiento farmacológico , Modelos Animales de Enfermedad , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismoRESUMEN
Drug repurposing is a promising approach to identify new pharmacological indications for drugs that have already been established. However, there is still a limitation in the availability of a high-throughput in vivo preclinical system that is suitable for screening and investigating new pharmacological indications. The aim of this study was to introduce the application of Drosophila larvae as an in vivo platform to screen drug candidates with anti-aging and immunomodulatory activities. To determine whether Drosophila larvae can be utilized for assessing anti-aging and immunomodulatory activities, phenotypical and molecular assays were conducted using wildtype and mutant lines of Drosophila. The utilization of mutant lines (PGRP-LBΔ and Psh[1];;ModSP[KO]) mimics the autoinflammatory and immunodeficient conditions in humans, thereby enabling a thorough investigation of the effects of various compounds. The phenotypical assay was carried out using survival and locomotor observation in Drosophila larvae and adult flies. Meanwhile, the molecular assay was conducted using the RT-qPCR method. In vivo survival analysis revealed that caffeine was relatively safe for Drosophila larvae and exhibited the ability to extend Drosophila lifespan compared to the untreated controls, suggesting its anti-aging properties. Further analysis using the RT-qPCR method demonstrated that caffeine treatment induced transcriptional changes in the Drosophila larvae, particularly in the downstream of NF-κB and JAK-STAT pathways, two distinct immune-related pathways homologue to humans. In addition, caffeine enhanced the survival of Drosophila autoinflammatory model, further implying its immunosuppressive activity. Nevertheless, this compound had minimal to no effect on the survival of Staphylococcus aureus-infected wildtype and immunodeficient Drosophila, refuting its antibacterial and immunostimulant activities. Overall, our results suggest that the anti-aging and immunosuppressive activities of caffeine observed in Drosophila larvae align with those reported in mammalian model systems, emphasizing the suitability of Drosophila larvae as a model organism in drug repurposing endeavors, particularly for the screening of newly discovered chemical entities to assess their immunomodulatory activities before proceedings to investigations in mammalian animal models.
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Envejecimiento , Cafeína , Larva , Animales , Larva/efectos de los fármacos , Larva/inmunología , Cafeína/farmacología , Envejecimiento/efectos de los fármacos , Envejecimiento/inmunología , Drosophila/efectos de los fármacos , Drosophila melanogaster/efectos de los fármacos , Drosophila melanogaster/inmunología , Drosophila melanogaster/microbiologíaRESUMEN
A nutritional approach could be a promising strategy to prevent or decrease the progression of neurodegenerative disorders such as Parkinson's disease (PD). The neuroprotective role of walnut oil (WO) was investigated in Drosophila melanogaster treated with rotenone (Rot), as a PD model, WO, or their combination, and compared to controls. WO reduced mortality and improved locomotor activity impairment after 3 and 7 days, induced by Rot. LC-MS analyses of fatty acid levels in Drosophila heads showed a significant increase in linolenic (ALA) and linoleic acid (LA) both in flies fed with the WO-enriched diet and in those treated with the association of WO with Rot. Flies supplemented with the WO diet showed an increase in brain dopamine (DA) level, while Rot treatment significantly depleted dopamine content; conversely, the association of Rot with WO did not modify DA content compared to controls. The greater intake of ALA and LA in the enriched diet enhanced their levels in Drosophila brain, suggesting a neuroprotective role of polyunsaturated fatty acids against Rot-induced neurotoxicity. The involvement of the dopaminergic system in the improvement of behavioral and biochemical parameters in Drosophila fed with WO is also suggested.
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Modelos Animales de Enfermedad , Drosophila melanogaster , Juglans , Enfermedad de Parkinson , Aceites de Plantas , Animales , Drosophila melanogaster/efectos de los fármacos , Juglans/química , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/metabolismo , Aceites de Plantas/farmacología , Aceites de Plantas/química , Dopamina/metabolismo , Rotenona , Encéfalo/metabolismo , Encéfalo/efectos de los fármacos , Fármacos Neuroprotectores/farmacologíaRESUMEN
BACKGROUND: Parkinson's disease (PD), the most prevalent type of Parkinsonism, is a progressive neurological condition characterized by a range of motor and non-motor symptoms. The complicated etiology of PD is thought to involve a summation of aging, genetic predisposition, and environmental variables. However, the α-synuclein protein plays a significant role in the disease's pathophysiology. MATERIALS AND METHODS: The UAS-α-Syn and Ddc-Gal4 strains were crossed to produce offspring referred to as PD flies. The entire population of flies was divided into five groups, each having about 100 flies and five replicates. The control group (w1118) and the PD group not receiving treatment were exposed to lauric acid (LA)/levodopa (LD)-free diet, while the PD groups that received treatments were fed with either a 250 mg/kg LA diet, a 250 mg/kg LD diet, or a combination of the two for 21 days. Longevity, geotaxis, and olfactory assays were performed in addition to other biochemical tests. RESULTS: As a result of the overexpression of α-synuclein, the locomotive capacity, lifespan, and antioxidant status were all significantly (p < .05) reduced, and the apoptotic and neuroinflammatory activities were increased. Nevertheless, the majority of the treated flies improved significantly (p < .05). CONCLUSION: LA, whether combined with LD or not, elicited a significant response in α-synuclein/dopa decarboxylase genetically modified Drosophila melanogaster Parkinsonism models.
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Apoptosis , Modelos Animales de Enfermedad , Drosophila melanogaster , Ácidos Láuricos , Levodopa , Trastornos Parkinsonianos , Animales , Drosophila melanogaster/efectos de los fármacos , Ácidos Láuricos/farmacología , Ácidos Láuricos/administración & dosificación , Trastornos Parkinsonianos/tratamiento farmacológico , Trastornos Parkinsonianos/metabolismo , Levodopa/farmacología , Levodopa/administración & dosificación , Apoptosis/efectos de los fármacos , alfa-Sinucleína/metabolismo , Animales Modificados Genéticamente , Estrés Oxidativo/efectos de los fármacos , Longevidad/efectos de los fármacos , MasculinoRESUMEN
Neurons rely on mitochondrial energy metabolism for essential functions like neurogenesis, neurotransmission, and synaptic plasticity. Mitochondrial dysfunctions are associated with neurodevelopmental disorders including Fragile X syndrome (FXS), the most common cause of inherited intellectual disability, which also presents with motor skill deficits. However, the precise role of mitochondria in the pathophysiology of FXS remains largely unknown. Notably, previous studies have linked the serotonergic system and mitochondrial activity to FXS. Our study investigates the potential therapeutic role of serotonin receptor 1A (5-HT1A) in FXS. Using the Drosophila model of FXS, we demonstrated that treatment with eltoprazine, a 5-HT1A agonist, can ameliorate synaptic transmission, correct mitochondrial deficits, and ultimately improve motor behavior. While these findings suggest that the 5-HT1A-mitochondrial axis may be a promising therapeutic target, further investigation is needed in the context of FXS.
Asunto(s)
Modelos Animales de Enfermedad , Síndrome del Cromosoma X Frágil , Mitocondrias , Receptor de Serotonina 5-HT1A , Animales , Síndrome del Cromosoma X Frágil/tratamiento farmacológico , Síndrome del Cromosoma X Frágil/metabolismo , Receptor de Serotonina 5-HT1A/metabolismo , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Drosophila , Piperazinas/farmacología , Transmisión Sináptica/efectos de los fármacos , Agonistas del Receptor de Serotonina 5-HT1/farmacología , Agonistas del Receptor de Serotonina 5-HT1/uso terapéutico , Drosophila melanogaster/efectos de los fármacos , Actividad Motora/efectos de los fármacosRESUMEN
Nutrition and resilience are linked, though it is not yet clear how diet confers stress resistance or the breadth of stressors that it can protect against. We have previously shown that transiently restricting an essential amino acid can protect Drosophila melanogaster against nicotine poisoning. Here, we sought to characterize the nature of this dietary-mediated protection and determine whether it was sex, amino acid and/or nicotine specific. When we compared between sexes, we found that isoleucine deprivation increases female, but not male, nicotine resistance. Surprisingly, we found that this protection afforded to females was not replicated by dietary protein restriction and was instead specific to individual amino acid restriction. To understand whether these beneficial effects of diet were specific to nicotine or were generalizable across stressors, we pre-treated flies with amino acid restriction diets and exposed them to other types of stress. We found that some of the diets that protected against nicotine also protected against oxidative and starvation stress, and improved survival following cold shock. Interestingly, we found that a diet lacking isoleucine was the only diet to protect against all these stressors. These data point to isoleucine as a critical determinant of robustness in the face of environmental challenges.
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Drosophila melanogaster , Nicotina , Estrés Fisiológico , Animales , Drosophila melanogaster/efectos de los fármacos , Femenino , Masculino , Nicotina/farmacología , Estrés Fisiológico/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Aminoácidos/farmacología , Aminoácidos/metabolismo , Isoleucina/farmacologíaRESUMEN
BACKGROUND: Many common diseases exhibit uncontrolled mTOR signaling, prompting considerable interest in the therapeutic potential of mTOR inhibitors, such as rapamycin, to treat a range of conditions, including cancer, aging-related pathologies, and neurological disorders. Despite encouraging preclinical results, the success of mTOR interventions in the clinic has been limited by off-target side effects and dose-limiting toxicities. Improving clinical efficacy and mitigating side effects require a better understanding of the influence of key clinical factors, such as sex, tissue, and genomic background, on the outcomes of mTOR-targeting therapies. RESULTS: We assayed gene expression with and without rapamycin exposure across three distinct body parts (head, thorax, abdomen) of D. melanogaster flies, bearing either their native melanogaster mitochondrial genome or the mitochondrial genome from a related species, D. simulans. The fully factorial RNA-seq study design revealed a large number of genes that responded to the rapamycin treatment in a sex-dependent and tissue-dependent manner, and relatively few genes with the transcriptional response to rapamycin affected by the mitochondrial background. Reanalysis of an earlier study confirmed that mitochondria can have a temporal influence on rapamycin response. CONCLUSIONS: We found significant and wide-ranging effects of sex and body part, alongside a subtle, potentially time-dependent, influence of mitochondria on the transcriptional response to rapamycin. Our findings suggest a number of pathways that could be crucial for predicting potential side effects of mTOR inhibition in a particular sex or tissue. Further studies of the temporal response to rapamycin are necessary to elucidate the effects of the mitochondrial background on mTOR and its inhibition.
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Mitocondrias , Sirolimus , Animales , Sirolimus/farmacología , Femenino , Masculino , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Mitocondrias/genética , Drosophila melanogaster/genética , Drosophila melanogaster/efectos de los fármacos , Factores Sexuales , Serina-Treonina Quinasas TOR/metabolismo , Especificidad de Órganos/genética , Drosophila/genética , Drosophila/efectos de los fármacos , Transcripción Genética/efectos de los fármacos , Perfilación de la Expresión GénicaRESUMEN
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 7 days. Posteriorly, their offspring were exposed to a diet containing lutein-loaded nanoparticles for a period of 24 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.
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Conducta Animal , Drosophila melanogaster , Luteína , Nanopartículas , Nitrocompuestos , Animales , Drosophila melanogaster/efectos de los fármacos , Luteína/farmacología , Luteína/administración & dosificación , Conducta Animal/efectos de los fármacos , Masculino , Femenino , Nitrocompuestos/toxicidad , Neonicotinoides/toxicidad , Estrés Oxidativo/efectos de los fármacos , Insecticidas/toxicidad , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/administración & dosificación , Trastornos del Neurodesarrollo/prevención & control , Trastornos del Neurodesarrollo/inducido químicamente , Trastornos del Neurodesarrollo/metabolismo , Antioxidantes/farmacología , Antioxidantes/metabolismoRESUMEN
The minute wasp Habrobracon hebetor venom (HH venom) is a potent cocktail of toxins that paralyzes the victim's muscles and suppresses humoral and cellular immunity. This study examined the effect of HH venom on specific biochemical, physiological, and ultrastructural characteristics of the thoracic and nervous (CNS) tissues of Drosophila melanogaster under in vitro conditions. Venom treatment modulated the activities of superoxide dismutase (SOD) and catalase (CAT), endogenous Drome-AKH level, and affected the relative viability of the cells. Additionally, it reduced the expression of genes related to the immune system in the CNS, including Keap1, Relish, Nox, Eiger, Gadd45, and Domeless, as well as in the thoracic muscles, except for Nox. Besides, venom treatment led to deteriorative changes in the ultrastructure of muscle cells, particularly affecting the mitochondria. When venom and Drosophila melanogaster-adipokinetic hormone (Drome-AKH) were applied together, the effects of the venom alone were often modulated. The harmful effect of the venom on SOD activity was relatively reduced and the activity returned to a level similar to that of the control. In the CNS, the simultaneous application of venom and hormones abolished the suppression of previously reported immune-related genes (except for Gadd45), whereas in the muscles, this was only true for Eiger. Additionally, Drome-AKH restored cell structure to a level comparable to that of the control and lessened the harmful effects of HH venom on muscle mitochondria. These findings suggest a general body response of D. melanogaster to HH venom and a partial defensive role of Drome-AKH in this process.
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Proteínas de Drosophila , Drosophila melanogaster , Hormonas de Insectos , Oligopéptidos , Ácido Pirrolidona Carboxílico , Venenos de Avispas , Avispas , Animales , Drosophila melanogaster/efectos de los fármacos , Venenos de Avispas/toxicidad , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/genética , Avispas/efectos de los fármacos , Hormonas de Insectos/metabolismo , Oligopéptidos/farmacología , Oligopéptidos/toxicidad , Ácido Pirrolidona Carboxílico/análogos & derivados , Superóxido Dismutasa/metabolismo , Catalasa/metabolismo , Catalasa/genética , Sistema Nervioso Central/efectos de los fármacosRESUMEN
Previous studies have demonstrated the efficacy of betahistine mesylate in treating vertigo and angioneurotic headache, enhancing microcirculation, and facilitating histamine release. However, limited research has been conducted on the drug's potential in mitigating blue light-induced damage. Thus, this study utilized Drosophila as the model organism and employed the Siler model to investigate the impact of various concentrations of betahistine mesylate on the lifespan, under 3000 lx blue light irradiation. At the same time we measure food intake, spontaneous activity, and sleep duration of Drosophila. The findings of this study indicate that a high concentration of betahistine mesylate can decrease the initial mortality (b0) in male flies, mitigating the damage of blue light to Drosophila. Consequently, this delays the aging process in male Drosophila and extends their average lifespan. After betahistine mesylate ingestion, locomotor activity upon blue light exposure decreased significantly in male Drosophila. In conclusion, this study offers initial evidence supporting the investigation of the regulatory mechanisms of betahistine mesylate on lifespan and its potential anti-blue light effects.
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Betahistina , Luz , Animales , Betahistina/farmacología , Masculino , Drosophila/efectos de los fármacos , Femenino , Drosophila melanogaster/efectos de los fármacos , Drosophila melanogaster/efectos de la radiación , Longevidad/efectos de los fármacos , Longevidad/efectos de la radiación , Sueño/efectos de los fármacos , Sueño/efectos de la radiación , Modelos Animales , Luz AzulRESUMEN
Calcium oxalate (CaOx) kidney stones accumulate within the renal tubule due to high concentrations of insoluble deposits in the urine. Pb2+-induced Ca2+ mobilization along with Pb2+-induced nephrotoxic effects within the proximal tubule have been well established; however, Pb2+ mediated effects within the collecting duct remains insufficiently studied. Thus in vitro and ex vivo model systems were treated with increasing concentrations of lead (II) acetate (PbAc) ± sodium oxalate (Na2C2O4) for 1 h, both individually and in combination. Pb2+-mediated solution turbidity increased 2 to 5 times greater post-exposure to 75, 100 and 200 µM Pb2+ with the additional co-treatment of 10 mM oxalate in mouse inner medullary collecting duct (mIMCD-3) cells. Additionally, 100 µM and 200 µM Pb2+ alone induced significant levels of intracellular Ca2+ release. To validate Pb2+-mediated effects on the formation of CaOx crystals, alizarin red staining confirmed the presence of CaOx crystallization. Pb2+-induced intracellular Ca2+ was also observed ex vivo in fly Malpighian tubules with significant increases in CaOx crystal formation via Pb2+-induced intracellular Ca2+ release significantly increasing the average crystal number, size, and total area of crystal formation, which was ameliorated by tissue-specific SPoCk C transporter and Capa receptor knockdown. These studies demonstrate Pb2+-induced Ca2+ release likely increases the formation of CaOx crystals, which is modulated by a Gq-linked mechanism with concurrent Ca2+ extracellular mobilization.
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Oxalato de Calcio , Cristalización , Drosophila melanogaster , Túbulos Renales Colectores , Plomo , Nefrolitiasis , Animales , Oxalato de Calcio/química , Oxalato de Calcio/metabolismo , Drosophila melanogaster/efectos de los fármacos , Túbulos Renales Colectores/metabolismo , Túbulos Renales Colectores/efectos de los fármacos , Túbulos Renales Colectores/patología , Ratones , Plomo/toxicidad , Nefrolitiasis/metabolismo , Calcio/metabolismo , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/genética , Modelos Animales de Enfermedad , Línea Celular , Técnicas de Silenciamiento del GenRESUMEN
Across the globe, many species of insects are facing population decline. This is largely driven by anthropogenic changes to the environment, including the widespread exposure of invertebrates to endocrine disrupting chemicals (EDCs), which impair fertility. To test whether generations of Drosophila melanogaster born from parents exposed to a common dietary EDC, equol, could recover reproductive function, we quantified the reproductive capacity of the two subsequent generations. Using a novel suite of flow cytometry assays to assess sperm functionality in real time, we find that sperm function is compromised across three generations, even after non-exposed in individuals contribute to the breeding population. Though the sex ratio alters in response to EDC exposure, favouring the survival of female offspring, most lineages with ancestral EDC exposure exhibit persistent subfertility in both the male and female. Male offspring with ancestral EDC exposure present with reduced fertility and dysfunctional spermatozoa, whereby spermatozoa are metabolically stressed, lack DNA integrity and present with permanent epigenetic alterations. Across generations, male and female offspring demonstrate distinct patterns of reproductive characteristics, depending upon the specific lineage of EDC exposure. Our results illustrate how dietary EDCs present in agricultural plants could promote transgenerational subfertility and contribute to declining insect populations.
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Drosophila melanogaster , Disruptores Endocrinos , Fertilidad , Espermatozoides , Animales , Masculino , Disruptores Endocrinos/toxicidad , Femenino , Drosophila melanogaster/efectos de los fármacos , Espermatozoides/efectos de los fármacos , Fertilidad/efectos de los fármacos , Exposición Dietética/efectos adversos , Infertilidad/inducido químicamente , Reproducción/efectos de los fármacos , Epigénesis Genética/efectos de los fármacos , Razón de MasculinidadRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Hancornia speciosa is a medicinal plant popularly used to treat different medical issues, including infectious diseases. Exploring the therapeutic potentialities of the extracts from medicinal plants combined with conventional antibiotic drugs is a promising horizon, especially considering the rising microbial resistance. AIM OF THE STUDY: This study aimed to characterize the chemical composition of the ethereal (EEHS) and methanolic (MEHS) extracts of the stem bark of H. speciosa, and also evaluate their antibacterial and drug-modifying activity, and toxicity. MATERIALS AND METHODS: The extracts were characterized by gas chromatography coupled to mass spectrometry (GC-MS). Additionally, total phenol and flavonoid contents were determined. The antibacterial and antibiotic-modifying activity was evaluated against strains of Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa using the serial microdilution method, obtaining the minimum inhibitory concentration (MIC). The toxicity assay was carried out using the Drosophila melanogaster model. RESULTS: Thirty compounds were identified in the extracts of the stem bark of H. speciosa, with triterpenoids being predominant in both extracts. Additionally, fatty alcohols, carbohydrates, fatty acids, phenolic acids, and phytosterols were identified in both extracts. EEHS and MEHS extracts had considerable phenol contents (346.4 and 340.0 mg GAE/g, respectively). Flavonoids were detected in a lower proportion (7.6 and 6.9 mg QE/g, respectively). H. speciosa extracts did not display intrinsic antibacterial activity against the bacterial strains evaluated, however, they were capable of modifying the activity of gentamicin, erythromycin, and norfloxacin. EEHS increased the efficacy of norfloxacin against E. coli and S. aureus, reducing MIC values by 50%. MEHS potentiated the action of gentamicin against all bacterial strains, especially against E. coli. The extracts did not display toxicity at clinically relevant concentrations against D. melanogaster. CONCLUSION: The stem bark of H. speciosa was considered a rich source of bioactive compounds. Our findings evidenced the therapeutic potential of H. speciosa extracts for the development of new pharmaceutical therapeutics against bacteria. Although the extracts did not exhibit intrinsic antibacterial activity, they enhanced the efficacy of commercial antibiotic drugs and were non-toxic at clinically relevant concentrations. Future studies are needed to elucidate the mechanisms of action of these extracts, ensuring their safety and efficacy.
Asunto(s)
Antibacterianos , Apocynaceae , Pruebas de Sensibilidad Microbiana , Corteza de la Planta , Extractos Vegetales , Extractos Vegetales/farmacología , Extractos Vegetales/toxicidad , Extractos Vegetales/química , Antibacterianos/farmacología , Antibacterianos/toxicidad , Antibacterianos/química , Corteza de la Planta/química , Animales , Apocynaceae/química , Staphylococcus aureus/efectos de los fármacos , Drosophila melanogaster/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Pseudomonas aeruginosa/efectos de los fármacos , Tallos de la Planta/química , Cromatografía de Gases y Espectrometría de MasasRESUMEN
The Advanced Oxidative Processes have demonstrated potential for application in the degradation of organic pollutants, such as Paraquat (PQ) from water and wastewater, due to their low price, high efficiency, and non-toxic properties. In this study, we investigated whether the photodegradation of PQ with TiO2 nanotubes reduced its toxicity in Drosophila melanogaster. However, dietary ingestion of degradation products PQ for larvae resulted in a low axial ratio (pupal volume). In the adults, products of photodegradation of PQ exposure markedly diminished climbing ability in a time-dependent manner after 10 days of feeding. In addition, exposure of D. melanogaster to photodegradation of PQ reduced acetylcholinesterase and citrate synthase activities but improved oxidative stress, as evidenced by oxide nitric, protein carbonyl, and lactate production. These results suggest that the photodegradation of PQ with TiO2 nanotubes produced PQ fragments with higher toxicity than PQ, while the precise mechanism of its action needs further investigation.
Asunto(s)
Drosophila melanogaster , Paraquat , Titanio , Animales , Drosophila melanogaster/efectos de los fármacos , Paraquat/toxicidad , Titanio/toxicidad , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/efectos de la radiación , Acetilcolinesterasa/metabolismo , Herbicidas/toxicidad , Herbicidas/efectos de la radiación , Nanotubos/química , Nanotubos/toxicidad , Conducta Animal/efectos de los fármacos , Conducta Animal/efectos de la radiación , Larva/efectos de los fármacos , Catálisis , Carbonilación Proteica/efectos de los fármacosRESUMEN
Geometric morphometrics analysis (GMA) is a well-known technique to identify minute changes in Drosophila wings. This study aimed to determine potential changes in Drosophila wings shape and size after exposure to polystyrene nanoplastics (NPs) (50 nm) and microplastics (MPs) (1 µm). Flies were exposed from eggs to pupal eclosion and analyzed using GMA. Results revealed a difference in shape and size between male and female wings, as expected, due to sexual dimorphism. Therefore, wings were analyzed by sex. Wings of MPs and NPs treated females were elongated compared to controls and had a constriction of the wing joint. Additionally, MPs treated female flies had the most dissimilar shape compared to controls. In male flies, NPs flies had smaller wings compared to MPs and control flies. Compared to control, NPs wings of males were shrunken at the joint and in the entire proximal region of the wing. However, male MPs wings had a narrower anal region and were slightly elongated. These results reveal that wing shape and size can change in a different way based on the sex of the flies and size of plastic particles that larvae interacted with. All the changes in the wings occurred only within the normally allowed wing variation and treatment with NPs/MPs did not cause development of the aberrant phenotypes. Results can pave the way for further understanding of how MPs and NPs can alter phenotypes of flies.
Asunto(s)
Microplásticos , Alas de Animales , Animales , Alas de Animales/anatomía & histología , Alas de Animales/efectos de los fármacos , Masculino , Femenino , Microplásticos/toxicidad , Nanopartículas/toxicidad , Larva/efectos de los fármacos , Larva/anatomía & histología , Drosophila/anatomía & histología , Drosophila/efectos de los fármacos , Caracteres Sexuales , Poliestirenos , Drosophila melanogaster/efectos de los fármacos , Drosophila melanogaster/anatomía & histologíaRESUMEN
Hyperglycaemia-induced oxidative stress plays significant roles in the development of type 2 diabetes and its complications. This study investigates effects of magainin-AM2 on high-sucrose diet induced redox imbalance and cognitive impairment in Drosophila melanogaster. Effects of various concentrations of sucrose, magainin-AM2 or a combination of both agents on mortality, eclosion rate, generation of reactive oxygen and nitrogen species, activities of antioxidant enzymes, thiol system, and markers of cognitive functions in control and treated flies were examined. Results showed that the exposure of flies to high sucrose (30 %-60 % w/w) diet increased mortality rate (38-67 %, P < 0.001) and levels of glucose (1.8-1.9-fold, P < 0.001), hydrogen peroxide (1.4-1.5-fold, P < 0.01) and nitrite/nitrate (1.2-fold, P < 0.01). Decreased levels of total thiol (53-59 %, P < 0.01), non-protein thiols (59-63 %, P < 0.01), catalase activities (39-47 %, P < 0.01-0.05) and glutathione-s-transferase activities (31-43 %, P < 0.01-0.05) were also observed. Magainin-AM2 (0-10 µM/kg diet) did not affect fly mortality rate, levels of hydrogen peroxide and nitrite/nitrate, and activities of catalase and glutathione-s-transferase. However, the peptide produced a dose-dependent increase in total thiol 1.2-1.6-fold, P < 0.001-0.01)and increases non-protein thiol levels at 10 µM/kg diet (2.0-fold, P < 0.01). Magainin-AM2 inhibited sucrose-induced elevation of glucose (55-70 %, P < 0.001), hydrogen peroxide (11-12 %, P < 0.01) and nitrite/nitrate (20-34 %, P < 0.01-0.05). The peptide prevented sucrose-induced reduction in total and non-protein thiols (1.9-2.0-fold, P < 0.05) levels and activities of catalase (2.3-3.1-fold, P < 0.001) and glutathione-s-transferase (1.8-2.8-fold, P < 0.001-0.05). Magainin-AM2 inhibited sucrose-induced reduction in acetylcholinesterase activities (3.6-4.0-fold, P < 0.001), eclosion rate (18 %, P < 0.001) and negative geotaxis (1.3-14-fold, P < 0.001). These results indicate that beneficial actions of magainin-AM2 may also involve the prevention of hyperglycaemia-induced oxidative damage and encourage its further development as an anti-diabetic agent.
Asunto(s)
Drosophila melanogaster , Hiperglucemia , Estrés Oxidativo , Sacarosa , Animales , Drosophila melanogaster/efectos de los fármacos , Drosophila melanogaster/metabolismo , Estrés Oxidativo/efectos de los fármacos , Hiperglucemia/metabolismo , Hiperglucemia/tratamiento farmacológico , Sacarosa/metabolismo , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/inducido químicamente , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/patología , Antioxidantes/farmacología , Antioxidantes/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Catalasa/metabolismo , Peróxido de Hidrógeno/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológicoRESUMEN
Chlorella pyrenoidos polysaccharides (CPPs) are the main active components of Chlorella pyrenoidos. They possess beneficial health properties, such as antioxidant, anti-inflammatory, and immune-enhancing. This study aims to investigate the protective function and mechanism of CPPs against high-temperature stress injury. Results showed that supplementation with 20 mg/mL CPPs significantly extended the lifespan of Drosophila melanogaster under high-temperature stress, improved its motility, and enhanced its resistance to starvation and oxidative stress. These effects were mainly attributed to the activation of Nrf2 signaling and enhanced antioxidant capacity. Additionally, it has been discovered that CPPs supplementation enhanced Drosophila resilience by preventing the disruption of the intestinal barrier and accumulation of reactive oxygen species caused by heat stress. Overall, these studies suggest that CPPs could be a useful natural therapy for preventing heat stress-induced injury.