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In this review we seek to systematically bring what has been published in the literature about the nervous system, endocrine system, neuroendocrine relationships, neuroendocrine modulations and endocrine disruptors in the alternative model Caenorhabditis elegans. The serotonergic, dopaminergic, GABAergic and glutamatergic neurotransmitters are related to the modulation of the neuroendocrine axis, leading to the activation or inhibition of several processes that occur in the worm through distinct and interconnected pathways. Furthermore, this review addresses the gut-neuronal axis as it has been revealed in recent years that gut microbiota impacts on neuronal functions. This review also approaches xenobiotics that can positively or negatively impact the neuroendocrine system in C. elegans as in mammals, which allows the application of this nematode to screen new drugs and to identify toxicants that are endocrine disruptors.
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Caenorhabditis elegans , Disruptores Endócrinos , Animais , Caenorhabditis elegans/metabolismo , Disruptores Endócrinos/farmacologia , Sistemas Neurossecretores , Sistema Nervoso , Neurônios , MamíferosRESUMO
In this study, we evaluated the toxicological and antiproliferative effects of B.â glabra Choisy bract extract (BGCE) in its free and loaded into liposomes forms administered to C.â elegans mutants with let-60 gain-of-function (gf). Our results demonstrated that the concentration up to 75â µg CAE/mL of BGCE was safe for the worms. Notably, we developed BGCE-loaded liposomes to extend the pharmacological window up to 100â µg CAE/mL without toxicity. In addition, the extract and liposomes reduced the number and area of the multivulva formed in let-60 gf mutants. There was also an increase in the apoptotic signaling in the germline cells and increased longevity mediated through DAF-16 nuclear translocation with GST-4 activation in the treated animals. Our findings demonstrated that the BGCE-loaded liposomes possess antitumoral effects due to the activation of the apoptotic signaling and DAF-16 nuclear translocation.
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Proteínas de Caenorhabditis elegans , Nyctaginaceae , Animais , Caenorhabditis elegans/fisiologia , Hiperplasia , LipossomosRESUMO
Campomanesia adamantium O. Berg. is a fruit tree species native to the Brazilian Cerrado biome whose fruits are consumed raw by the population. The present study determined the chemical composition of the C. adamantium fruit pulp (FPCA) and investigated its in vitro antioxidant potential and its biological effects in a Caenorhabditis elegans model. The chemical profile obtained by LC-DAD-MS identified 27 compounds, including phenolic compounds, flavonoids, and organic carboxylic acids, in addition to antioxidant lipophilic pigments and ascorbic acid. The in vitro antioxidant activity was analysed by the radical scavenging method. In vivo, FPCA showed no acute reproductive or locomotor toxicity. It promoted protection against thermal and oxidative stress and increased the lifespan of C. elegans. It also upregulated the antioxidant enzymes superoxide dismutase and glutathione S-transferase and activated the transcription factor DAF-16. These results provide unprecedented in vitro and in vivo evidence for the potential functional use of FPCA in the prevention of oxidative stress and promotion of longevity.
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Proteínas de Caenorhabditis elegans , Myrtaceae , Animais , Antioxidantes/farmacologia , Caenorhabditis elegans/metabolismo , Longevidade , Brasil , Frutas/metabolismo , Extratos Vegetais/química , Estresse Oxidativo , Myrtaceae/química , Proteínas de Caenorhabditis elegans/metabolismoRESUMO
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been widely used due to its specific and reproducible neurotoxic effect on the nigrostriatal system, being considered a convenient model of dopaminergic neurodegeneration to study interventions therapeutics. The purple pitanga (Eugenia uniflora) is a polyphenol-rich fruit with antioxidant and antidepressant properties, among others. Therefore, this study investigated the effect of purple pitanga extract (PPE) on acute early oxidative stress induced by intranasal 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration in rats. Male Wistar rats were pre-treated orally with PPE (1000 mg/kg) or vehicle. After 24 h, MPTP (0.1 mg/10µL/nostril) or vehicle was administered bilaterally into the animal's nostrils, and 6 h later, the olfactory bulb (OB), striatum (ST), and substantia nigra (SN) were collected to evaluate the oxidative stress parameters. Our findings revealed that OB and SN were the most affected areas after 6 h of MPTP infusion; an early increase in reactive oxygen species (ROS) levels was observed, while pretreatment with a single dose of PPE prevented this increment. No differences in thiobarbituric acid reactive species (TBARS) and 3-nitrotyrosine (3-NT) formation were observed, although 4-hydroxy-2-nonenal (4-HNE) levels increased, which is the most toxic form of lipid peroxidation, in the MPTP group. The PPE pretreatment could prevent this increase by increasing the NPSH levels previously decreased by MPTP. Furthermore, PPE prevents the Na+/K + ATPase strongly inhibited by MPTP, showing the neuroprotective capacity of the PPE by inhibiting the MPTP-generated oxidation. Thus, we demonstrated for the first time the antioxidant and neuroprotective effects of PPE against the early MPTP neurotoxicity.
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Eugenia , Fármacos Neuroprotetores , Ratos , Masculino , Animais , Camundongos , Antioxidantes/farmacologia , Antioxidantes/metabolismo , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/farmacologia , Eugenia/metabolismo , Ratos Wistar , Estresse Oxidativo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Substância Negra/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Camundongos Endogâmicos C57BL , Modelos Animais de DoençasRESUMO
Alzheimer's disease (AD) is the most common form of dementia in older people, and available treatments are palliative and produce undesirable side effects. The 4-phenyltellanyl-7-chloroquinoline (TQ) is an organochalcogen compound studied due to its pharmacological properties, particularly its antioxidant potential. However, TQ possesses some drawbacks such as low aqueous solubility and high toxicity, thus warranting the search for tools that improve the safety and effectiveness of new compounds. Here, we developed and investigated the biological effects of TQ-loaded polymeric nanocapsules (NCTQ) in an AD model in transgenic Caenorhabditis elegans expressing human Aß1-42 in their body-wall muscles and Swiss mice injected with Aß25-35. The NCTQ displayed good physicochemical properties, including nanometer size and maximum encapsulation capacity. The treatment showed low toxicity, reduced Aß peptide-induced paralysis, and activated an endoplasmic reticulum chaperone in the C. elegans model. The Aß injection in mice caused memory impairment, which NCTQ mitigated by improving working, long-term, and aversive memory. Additionally, no changes in biochemical markers were evidenced in mice, demonstrating that there was no hepatotoxicity in the tested doses. Altogether, these findings provide insights into the neuroprotective effects of TQ and indicate that NCTQ is a promising candidate for AD treatment.
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Iron oxide nanoparticles present superparamagnetic properties that enable their application in various areas, including drug delivery at specific locations in the organism. Silver nanoparticles have potent antimicrobial effects. Although the combination of Fe3O4-NPs and Ag-NPs in one hybrid nanostructure (Fe3O4@Ag-NPs) demonstrated promising targeted biomedical applications, their toxicological effects are unknown and need to be assessed. Caenorhabditis elegans is a promising model for nanotoxicological analysis, as it allows an initial screening of new substances. After exposure to Fe3O4-NPs, Ag-NPs and Fe3O4@Ag-NPs, we observed that hybrid NPs reduced the C. elegans survival and reproduction. Higher concentrations of Fe3O4@Ag-NPs caused an increase in cell apoptosis in the germline and a decrease in egg laying, which was associated with a decrease in worm swimming movements and abnormalities in the cholinergic neurons. Fe3O4@Ag-NPs caused an increase in reactive oxygen species, along with activation of DAF-16 transcription factor. A higher expression of the target genes GST-4::GFP and SOD-3::GFP were evidenced, which suggests the activation of the antioxidant system. Our results indicate the reprotoxicity caused by high levels of Fe3O4@Ag-NPs, as well as cholinergic neurotoxicity and activation of the antioxidant system in C. elegans, suggesting that high concentrations of these nanomaterials can be harmful to living organisms.
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Nanopartículas Metálicas , Nanopartículas , Animais , Caenorhabditis elegans , Nanopartículas Metálicas/química , Prata/química , Antioxidantes/farmacologia , Nanopartículas/toxicidadeRESUMO
Bladder cancer is the fourth most common malignancy in men. It can present along the entire continuum of severity, from mild to well-differentiated disease to extremely malignant tumors with low survival rates. Human RAS genes are the most frequently mutated oncogenes in human cancers, and the critical role of aberrant Ras protein function in carcinogenesis is well established. Therefore, considerable efforts have been devoted to the development of anti-Ras inhibitors for cancer treatment. This study presents the biphenyl dihydropyrimidinone LaSOM 335 with high activity against T24 bladder cancer cells (IC50 = 10.73 ± 0.53 µM) and selectivity of cytotoxicity for this cancer cell line compared to two non-cancer cell lines investigated. Furthermore, we also show that this compound reduced vulvar development in the mutant let-60 gene of Caenorhabditis elegans. Let-60 is a homolog of the mammalian Ras gene. In addition, we observed that LaSOM 335 inhibits the enzymatic activity of CD73 and decreases CD73 expression. Possibly, this expression decrease is due to downstream EGFR signaling via the Ras-Raf-ERK pathway, that directly regulates CD73 expression via ERK1/2. Evidence suggests that non-immunomodulating functions of CD73 play an equally important role for cancer cell survival, progression, and migration. Regarding we also notice that LaSOM 335 was safe in the in vivo model of C. elegans. The set of these findings makes this biphenyl dihydropyrimidinone a promising candidate for further investigations in the bladder cancer field.
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Genes ras , Neoplasias da Bexiga Urinária , Masculino , Animais , Humanos , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Linhagem Celular Tumoral , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/metabolismo , 5'-Nucleotidase/genética , 5'-Nucleotidase/metabolismo , Mamíferos/genética , Mamíferos/metabolismoRESUMO
Quercetin is a flavonol widely distributed in plants and has various described biological functions. Several studies have reported on its ability to restore neuronal function in a wide variety of disease models, including animal models of neurodegenerative disorders such as Parkinson's disease. Quercetin per se can act as a neuroprotector/neuromodulator, especially in diseases related to impaired dopaminergic neurotransmission. However, little is known about how quercetin interacts with the dopaminergic machinery. Here we employed the nematode Caenorhabditis elegans to study this putative interaction. After observing behavioral modulation, mutant analysis and gene expression in C. elegans upon exposure to quercetin at a concentration that does not protect against MPTP, we constructed a homology-based dopamine transporter protein model to conduct a docking study. This led to suggestive evidence on how quercetin may act as a dopaminergic modulator by interacting with C. elegans' dopamine transporter and alter the nematode's exploratory behavior. Consistent with this model, quercetin controls C. elegans behavior in a way dependent on the presence of both the dopamine transporter (dat-1), which is up-regulated upon quercetin exposure, and the dopamine receptor 2 (dop-2), which appears to be mandatory for dat-1 up-regulation. Our data propose an interaction with the dopaminergic machinery that may help to establish the effects of quercetin as a neuromodulator.
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Dopamina , Quercetina , Transmissão Sináptica , Animais , Caenorhabditis elegans , Quercetina/farmacologia , Dopamina/metabolismo , Proteínas de Caenorhabditis elegans , Fármacos Neuroprotetores/farmacologia , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Neurônios/metabolismo , Estresse Oxidativo , Transmissão Sináptica/efeitos dos fármacos , Receptores de Dopamina D2/metabolismo , 1-Metil-4-Fenil-1,2,3,6-Tetra-HidropiridinaRESUMO
Nanoformulations containing zein nanoparticles (ZN) can promote the stability and protection of molecules with acaricidal activity. The present study sought to develop nanoformulations with ZN associated with cypermethrin (CYPE) + chlorpyrifos (CHLO) + a plant compound (citral, menthol or limonene), characterize them, and verify their efficacy against Rhipicephalus microplus ticks. Additionally, we aimed to assess its safety in nontarget nematodes found in soil at a site subjected to contamination by acaricides. The nanoformulations were characterized by dynamic light scattering and nanoparticle tracking analysis. Nanoformulations 1 (ZN+CYPE+CHLO+citral), 2 (ZN+CYPE+CHLO+menthol), and 3 (ZN+CYPE+CHLO+limonene) were measured for diameter, polydispersion, zeta potential, concentration, and encapsulation efficiency. Nanoformulations 1, 2, and 3 were evaluated in a range from 0.004 to 0.466 mg/mL on R. microplus larvae and caused mortality > 80% at concentrations above 0.029 mg/mL. The commercial acaricide Colosso® (CYPE 15 g + CHLO 25 g + citronellal 1 g) was evaluated also from 0.004 to 0.512 mg/mL and resulted in 71.9% larval mortality at 0.064 mg/mL. Formulations 1, 2, and 3 at 0.466 mg/mL showed acaricidal efficacy of 50.2%, 40.5%, and 60.1% on engorged females, respectively, while Colosso® at 0.512 mg/mL obtained only 39.4%. The nanoformulations exhibited long residual period of activity and lower toxicity to nontarget nematodes. ZN was able to protect the active compounds against degradation during the storage period. Thus, ZN can be an alternative for the development of new acaricidal formulations using lower concentrations of active compounds.
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Acaricidas , Rhipicephalus , Infestações por Carrapato , Zeína , Feminino , Animais , Acaricidas/farmacologia , Limoneno , Mentol , Larva , Infestações por Carrapato/prevenção & controle , Infestações por Carrapato/veterinária , Controle de Ácaros e CarrapatosRESUMO
Nanotechnology-based strategies have played a pivotal role in innovative products in different technological fields, including medicine, agriculture, and engineering. The redesign of the nanometric scale has improved drug targeting and delivery, diagnosis, water treatment, and analytical methods. Although efficiency brings benefits, toxicity in organisms and the environment is a concern, particularly in light of global climate change and plastic disposal in the environment. Therefore, to measure such effects, alternative models enable the assessment of impacts on both functional properties and toxicity. Caenorhabditis elegans is a nematode model that poses valuable advantages such as transparency, sensibility in responding to exogenous compounds, fast response to perturbations besides the possibility to replicate human disease through transgenics. Herein, we discuss the applications of C. elegans to nanomaterial safety and efficacy evaluations from one health perspective. We also highlight the directions for developing appropriate techniques to safely adopt magnetic and organic nanoparticles, and carbon nanosystems. A description was given of the specifics of targeting and treatment, especially for health purposes. Finally, we discuss C. elegans potential for studying the impacts caused by nanopesticides and nanoplastics as emerging contaminants, pointing out gaps in environmental studies related to toxicity, analytical methods, and future directions.
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Maca (Lepidium meyenii Walp.) has been used in folk medicine to treat fertility disturbances, a claim that has been evidenced in some studies. However, the clinical trials validating this use have shown paradoxical findings and then maca safety is not well known. This study investigated the effects and mechanisms by which maca affects the reproductive system using an in vivo model, the nematode Caenorhabditis elegans. Tuber maca powder, obtained from local commerce, was used to prepare the aqueous extract. Worms were acutely exposed to maca extracts (40, 120, 240, and 330 µg/µl), and 48 h after treatments, physiological and biochemical assays were conducted. Maca extract caused a significant decrease in total number of eggs and in the number of eggs per worm. These effects were associated to increased lipid peroxidation, reduced triacylglycerol levels, and also impaired vit-2 (vitellogenin) expression, besides increase in the number of apoptotic germline cells. We have found quantifiable levels of alkaloids in this maca extract, which presence could be related to this toxicity. Collectively, our data suggest that maca extract exposure causes reproductive toxicity to worms that could be, at least in part, associated to both an increase in apoptosis of germline cells and also to a decrease in vitellogenin expression, needed for egg yolk production and, consequently, successful reproduction.
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Lepidium , Extratos Vegetais , Animais , Extratos Vegetais/farmacologia , Caenorhabditis elegans , Peru , Vitelogeninas , ÁguaRESUMO
Nano-sized drug delivery systems have been the subject of intense research in recent years because polymeric materials allow the absorption and release of active substances in a controlled manner. Despite the benefits, the safety of nanoparticulate systems is an aspect to be understood, particularly in vivo systems. Caenorhabditis elegans is a very useful alternative model for nanotoxicology and has been recently applied in this field. The aim of this study was to evaluate toxicological endpoints in C. elegans exposed to nanocapsules (NC) prepared with different coatings: polysorbate 80 (NCP80); polyethylene glycol (NCPEG), Eudragit® RS 100 (NCEUD) and chitosan (NCCS). Nanocapsules were prepared by nanoprecipitation method and showed acceptable physico-chemical characterization. Polyethylene glycol nanocapsules and chitosan nanocapsules increased worms lethality in a dose-dependent manner in acute exposure; polysorbate 80 nanocapsules, polyethylene glycol nanocpsules and chitonan nanocapsules also increased lethality following chronic exposure. Chitosan nanocapsules were the most toxic in all exposures, demonstrating toxicity even at low concentrations. Reproduction and body length were not affected by any of the nanocapsules exposures. The expression of superoxide dismutase showed that polysorbate 80 nanocapsules at the highest concentration slightly increased SOD-3::GFP expression. On the other hand, chitosan nanocapsules exposure blunted SOD-3 expression. This work demonstrates the toxicological differences between nanocapsule produced with different coatings and indicates higher safety for the use of eugragit nanocapsule in new formulations for future drug delivery and targeting systems.
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Quitosana , Nanocápsulas , Animais , Nanocápsulas/toxicidade , Nanocápsulas/química , Caenorhabditis elegans , Quitosana/toxicidade , Polissorbatos/toxicidade , Polímeros/química , Superóxido DismutaseRESUMO
The existence of a formal Endocannabinoid System in C. elegans has been questioned due to data showing the absence of typical cannabinoid receptors in the worm; however, the presence of a full metabolism for endocannabinoids, alternative ligands, and receptors for these agents and a considerable number of orthologous and homologous genes regulating physiological cannabinoid-like signals and responses - several of which are similar to those of mammals - demonstrates a well-structured and functional complex system in nematodes. In this review, we describe and compare similarities and differences between the Endocannabinoid System in mammals and nematodes, highlighting the basis for the integral study of this novel system in the worm.
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Canabinoides , Endocanabinoides , Animais , Caenorhabditis elegans/metabolismo , Receptores de Canabinoides/metabolismo , Mamíferos/metabolismoRESUMO
OBJECTIVES: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the presence of aggregated amyloid-ß (Aß) peptides. Several natural compounds have been proposed against this disease and grape products are among these. However, little is known about grape juice potential. Transgenic Caenorhabditis elegans (C. elegans) strains that express human Aß have been used as an in vivo model for AD. METHODS: In this study, we have exposed CL2006 worms to nine different juices obtained from different cultivars. RESULTS: Cora, Bordo, Isabel, Isabel Precoce, BRS-Magna, BRS-Rubea and BRS-Violeta juices improved the behavioral phenotype (paralysis) that is caused by Aß aggregation in the transgenic animals at the concentrations tested and no toxic effects were found. Some juices were also able to increase the worm's lifespan. We could not attribute lifespan increase and paralysis reduction with any specific compound found in the phytochemical analysis. DISCUSSION: Our data indicate that the rich constitution of the juices is responsible for attenuating the phenotype caused by Aß aggregation in C. elegans.
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Doença de Alzheimer , Vitis , Animais , Humanos , Peptídeos beta-Amiloides/genética , Caenorhabditis elegans , Longevidade , Animais Geneticamente Modificados , Doença de Alzheimer/genética , Paralisia , Modelos Animais de DoençasRESUMO
In a previous in vitro study, dihydropyrimidinone-derived selenoesteres demonstrated antioxidant properties, metal chelators and inhibitory acetylcholinesterase (AChE) activity, making these compounds promising candidates for Alzheimer's Disease (AD) treatment. However, these effects have yet to be demonstrated in an in vivo animal model; therefore, this study aimed to evaluate the safety and efficacy of eight selenoester compounds in a Caenorhabditis elegans model using transgenic strains for amyloid-beta peptide (Aß) aggregation. The L1 stage worms were acutely exposed (30 min) to the compounds at concentrations ranging from 5 to 200 µM and after 48 h the maintenance temperature was increased to 25 ° C for Aß expression and aggregation. After 48 h, several parameters related to phenotypic manifestations of Aß toxicity and mechanistic elucidation were analyzed. At the concentrations tested no significant toxicity of the compounds was found. The selenoester compound FA90 significantly reduced the rate of paralyzed worms and increased the number of swimming movements compared to the untreated worms. In addition, FA90 and FA130 improved egg-laying induced by levamisole and positively modulated HSP-6 and HSP-4 expression, thereby increasing reticular and mitochondrial protein folding response in C. elegans, which could attenuate Aß aggregation in early exposure. Therefore, our initial screening using an alternative model demonstrated that FA90, among the eight selenoesters evaluated, was the most promising compound for AD evaluation screening in more complex animals.
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Peptídeos beta-Amiloides/antagonistas & inibidores , Fármacos Neuroprotetores/farmacologia , Compostos Organosselênicos/farmacologia , Pirimidinonas/farmacologia , Acetilcolinesterase/metabolismo , Peptídeos beta-Amiloides/metabolismo , Animais , Caenorhabditis elegans , Modelos Animais de Doenças , Levamisol/farmacologia , Fármacos Neuroprotetores/efeitos adversos , Organismos Geneticamente Modificados , Compostos Organosselênicos/efeitos adversos , Oviposição/efeitos dos fármacos , Pirimidinonas/efeitos adversosRESUMO
Uruguay River is the most important river in western Rio Grande do Sul, separating Brazil from Argentina and Uruguay. However, its pollution is of great concern due to agricultural activities in the region and the extensive use of pesticides. In a long term, this practice leads to environmental pollution, especially to the aquatic system. The objective of this study was to analyze the physicochemical characteristics, metals and pesticides levels in water samples obtained before and after the planting and pesticides' application season from three sites: Uruguay River and two minor affluents, Mezomo Dam and Salso Stream. For biomonitoring, the free-living nematode Caenorhabditis elegans was used, which were exposed for 24 h. We did not find any significant alteration in physicochemical parameters. In the pre- and post-pesticides' samples we observed a residual presence of three pesticides (tebuconazole, imazethapyr, and clomazone) and metals which levels were above the recommended (As, Hg, Fe, and Mn). Exposure to both pre- and post-pesticides' samples impaired C. elegans reproduction and post-pesticides samples reduced worms' survival rate and lifespan. PCA analysis indicated that the presence of metals and pesticides are important variables that impacted C. elegans biological endpoints. Our data demonstrates that Uruguay River and two affluents are contaminated independent whether before or after pesticides' application season. In addition, it reinforces the usefulness of biological indicators, since simple physicochemical analyses are not sufficient to attest water quality and ecological safety.
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Praguicidas , Poluentes Químicos da Água , Animais , Argentina , Monitoramento Biológico , Brasil , Caenorhabditis elegans , Monitoramento Ambiental , Praguicidas/análise , Praguicidas/toxicidade , Rios , Uruguai , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidadeRESUMO
The deficiency in the activity of the mitochondrial enzyme methylmalonyl-CoA mutase (MCM, EC 5.4.99.2) leads to a condition called methylmalonic academia, which is characterised by the accumulation of methylmalonic (MMA), malonic (MA) or other organic acids. Importantly, we have recently found that supplementation with Ilex paraguariensis aqueous extract offered protection against toxicity associated with MMA or MA exposure to Drosophila melanogaster. Of note, caffeic acid (CA) and caffeine (CAF) were the major phytochemicals found in our Ilex paraguariensis crude extract. Therefore, here, we have exploited CA and/or CAF to test the hypothesis that supplementation with the isolated compounds (either alone or combined) could exert a protective effect against MMA or MA-induced toxicity in flies. Therefore, flies were exposed to MA (5 mM) or MMA (5 mM) and concomitantly treated with CA (1.39 µg/mL), CAF (1.27 µg/mL) or CA + CAF for 10 days for survival, and for 4 days for behavioural and biochemical assays. CA, CAF and CA + CAF treatments completely abolished the mortality associated with either MMA or MA exposure. Moreover, CA and CAF, either alone or combined, completely abolished behavioural changes, and completely protect against changes in thiobarbituric acid reactive substances (TBARS) levels, catalase (CAT) activity and MTT reduction ability, associated with MA or MMA exposure. In turn, CAF restored SOD activity in the head of flies exposed to MA or MMA. However, CA and CAF (either alone or combined) significantly decreased acetylcholinesterase (AChE) activity per se, while CAF alone protected from changes in AChE activity (in head tissue) associated with MA or MMA. Finally, CA and/or CAF were able to protect from a decrease in glucose and triglyceride levels associated with both MA and MMA exposures in haemolymph. Together, our data confirm the hypothesis that supplementation with CA and/or CAF offers protection against detrimental changes associated with MMA or MA exposure in flies, being responsible, at least in part, for the protective effect of I. paraguariensis crude extract which was reported previously.
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Ácidos Cafeicos/farmacologia , Cafeína/farmacologia , Malonatos/toxicidade , Substâncias Protetoras/farmacologia , Acetilcolinesterase/metabolismo , Animais , Catalase/metabolismo , Drosophila melanogaster , Feminino , Glucose/metabolismo , Proteínas de Insetos/metabolismo , Locomoção/efeitos dos fármacos , Masculino , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Triglicerídeos/metabolismoRESUMO
Alzheimer's disease (AD) is a progressive brain disorder and complex mechanisms are involved in the physiopathology of AD. However, there is data suggesting that inflammation plays a role in its development and progression. Indeed, some non-steroidal anti-inflammatory drugs, such as meloxicam, which act by inhibiting cyclooxygenase-2 (COX-2) have been used as neuroprotective agents in different neurodegenerative disease models. The purpose of this study was to investigate the effects of co-nanoencapsulated curcumin and meloxicam in lipid core nanocapsules (LCN) on cognitive impairment induced by amyloid-beta peptide injection in mice. LCN were prepared by the nanoprecipitation method. Male Swiss mice received a single intracerebroventricular injection of amyloid-beta peptide aggregates (fragment 25-35, 3 nmol/3 µL) or vehicle and were subsequently treated with curcumin-loaded LCN (10 mg/kg) or meloxicam-loaded LCN (5 mg/kg) or meloxicam + curcumin-co-loaded LCN (5 and 10 mg/kg, respectively). Treatments were given on alternate days for 12 days (i.e., six doses, once every 48 hours, by intragastric gavage). Our data showed that amyloid-beta peptide infusion caused long-term memory deficits in the inhibitory avoidance and object recognition tests in mice. In the inhibitory avoidance test, both meloxicam and curcumin formulations (oil or co-loaded LCN) improved amyloid-beta-induced memory impairment in mice. However, only meloxicam and curcumin-co-loaded LCN attenuated non-aversive memory impairment in the object recognition test. Moreover, the beneficial effects of meloxicam and curcumin-co-loaded LCN could be explained by the anti-inflammatory properties of these drugs through cortical COX-2 downregulation. Our study suggests that the neuroprotective potential of meloxicam and curcumin co-nanoencapsulation is associated with cortical COX-2 modulation. This study was approved by the Committee on Care and Use of Experimental Animal Resources, the Federal University of Pampa, Brazil (approval No. 02-2015) on April 16, 2015.
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Fruits are sources of bioactive compounds that are responsible for several biological activities. Therefore, this study aimed to identify the chemical composition of the pulp of the Brazilian Savanna fruit Dipteryx alata; evaluate its toxic effects, influence on the life expectancy of the nematode Caenorhabditis elegans, and its antioxidant activities in vitro and in vivo; and describe the mechanisms involved. The chemical compounds identified include phenols, terpenes, fatty acid derivatives, vitamins, and a carboxylic acid. The in vitro antioxidant activity was demonstrated by radical scavenging methods. In vivo, the D. alata fruit pulp was not toxic and promoted resistance to oxidative stress in nematodes exposed to a chemical oxidizing agent. Furthermore, it promoted an increased life expectancy in wild-type nematodes and increased the expression of superoxide dismutase and the nuclear translocation of DAF-16. These results suggest that the beneficial effects identified are related to these two genes, which are involved in the regulation of metabolic activities, the control of oxidative stress, and the lifespan of C. elegans. These beneficial effects, which may be related to its chemical constituents, demonstrate its potential use as a functional and/or nutraceutical food.