RESUMO
Mycotoxins are toxic fungal metabolites and are responsible for contaminating several foods. The intake of foods contaminated by these substances is related to hepatotoxicity and carcinogenic effects, possibly due to increasing oxidative stress. The current study evaluated Pitaya fruit juice's antioxidant effects on oxidative damage aflatoxin B1 (AFB1)-induced. Rats received 1.5 mL of Pitaya juice via gavage (for 30 days), and on the 31st day, they received AFB1 (250 µg/kg, via gavage). Forty-eight hours after the AFB1 dose, rats were euthanized for dosages of alanine transaminase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP); dosage of oxidative markers (thiobarbituric acid reactive species (TBARS), reactive species (RS)) and antioxidant defenses (catalase (CAT), superoxide dismutase (SOD), Glutathione S-transferase (GST) activities and Glutathione (GSH)) levels in the liver; and detection of Heat shock protein 70 (Hsp-70) and nuclear factor- erythroid 2-related factor 2 (Nrf2) immunocontent in the liver. Our results indicated that the Pitaya juice reduced ALP activity. Further, rats exposed to AFB1 experienced liver damage due to the increase in TBARS, RS, and Hsp-70 and the reduction in CAT, GSH, and Nrf2. Pitaya juice could, however, protect against these damages. Finally, these results indicated that pre-treatment with Pitaya juice was effective against the oxidative damage induced. However, other aspects may be elucidated in the future to discover more targets of its action against mycotoxicosis.
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 , LactatosRESUMO
Iron (Fe) is used in various cellular functions, and a constant balance between its uptake, transport, storage, and use is necessary to maintain its homeostasis in the body. Changes in Fe metabolism with a consequent overload of this metal are related to neurological changes and cover a broad spectrum of diseases, mainly when these changes occur during the embryonic period. This work aimed to evaluate the effect of exposure to Fe overload during the embryonic period of Drosophila melanogaster. Progenitor flies (male and female) were exposed to ferrous sulfate (FeSO4) for ten days in concentrations of 0.5, 1, and 5 âmM. After mating and oviposition, the progenitors were removed and the treatment bottles preserved, and the number of daily hatches and cumulative hatching of the first filial generation (F1) were counted. Subsequently, F1 flies (separated by sex) were subjected to behavioral tests such as negative geotaxis test, open field test, grooming, and aggression test. They have evaluated the levels of dopamine (DA), serotonin (5-HT), octopamine (OA), tryptophan and tyrosine hydroxylase (TH), acetylcholinesterase, reactive species, and the levels of Fe in the progenitor flies and F1. The Fe levels of F1 flies are directly proportional to what is incorporated during the period of embryonic development; we also observed a delay in hatching and a reduction in the number of the hatch of F1 flies exposed during the embryonic period to the 5mM Fe diet, a fact that may be related to the reduction of the cell viability of the ovarian tissue of progenitor flies. The flies exposed to Fe (1 and 5 âmM) showed an increase in locomotor activity (hyperactivity) and a significantly higher number of repetitive movements. In addition to a high number of aggressive encounters when compared to control flies. We can also observe an increase in the levels of biogenic amines DA and 5-HT and an increase in TH activity in flies exposed to Fe (1 and 5 âmM) compared to the control group. We conclude that the hyperactive-like behavior demonstrated in both sexes by F1 flies exposed to Fe may be associated with a dysregulation in the levels of DA and 5-HT since Fe is a cofactor of TH, which had its activity increased in this study. Therefore, more attention is needed during the embryonic development period for exposure to Fe overload.
Assuntos
Drosophila melanogaster/embriologia , Hipercinese/fisiopatologia , Sobrecarga de Ferro/embriologia , Animais , Comportamento Animal/fisiologia , Aminas Biogênicas/metabolismo , Aminas Biogênicas/fisiologia , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Feminino , Expressão Gênica/genética , Regulação da Expressão Gênica no Desenvolvimento/genética , Hipercinese/etiologia , Ferro/metabolismo , Ferro/fisiologia , Ferro/toxicidade , Sobrecarga de Ferro/metabolismo , Sobrecarga de Ferro/fisiopatologia , Locomoção/efeitos dos fármacos , Masculino , Exposição Materna , Atividade Motora/efeitos dos fármacos , Oxirredução , Exposição PaternaRESUMO
The mechanisms underlying the neuroprotective effects of hesperidin in a murine model of PD are not fully elucidated. The current study was carried out to investigate the ability of hesperidin in modulating proinflammatory cytokines, neurotrophic factors, and neuronal recovery in 6-hydroxydopamine (6-OHDA)-induced nigral dopaminergic neuronal loss. Adult male C57BL/6 mice were randomly assigned into four groups: (I) sham/vehicle, (II) sham/hesperidin, (III) 6-OHDA/vehicle, and (IV) 6-OHDA/hesperidin. Mice received a unilateral intrastriatal injection of 6-OHDA and treated with hesperidin (50 mg/kg; per oral) for 28 days. After hesperidin treatment, mice were submitted to behavioral tests and had the striatum removed for neurochemical assays. Our results demonstrated that oral treatment with hesperidin ameliorated the anxiety-related and depressive-like behaviors in 6-OHDA-lesioned mice (p < 0.05). It also attenuated the striatal levels of proinflammatory cytokines tumor necrosis factor-α, interferon-gamma, interleukin-1ß, interleukin-2, and interleukin-6 and increased the levels of neurotrophic factors, including neurotrophin-3, brain-derived neurotrophic factor, and nerve growth factor in the striatum of 6-OHDA mice (p < 0.05). Hesperidin treatment was also capable to increase striatal levels of dopamine and its metabolite 3,4-dihydroxyphenylacetic acid and protects against the impairment of dopaminergic neurons in the substantia nigra pars compacta (SNpc) (p < 0.05). In conclusion, this study indicated that hesperidin exerts anxiolytic-like and antidepressant-like effect against 6-OHDA-induced neurotoxicity through the modulation of cytokine production, neurotrophic factors levels, and dopaminergic innervation in the striatum.
Assuntos
Comportamento Animal/efeitos dos fármacos , Corpo Estriado/efeitos dos fármacos , Citocinas/metabolismo , Neurônios Dopaminérgicos/efeitos dos fármacos , Hesperidina/farmacologia , Fatores de Crescimento Neural/metabolismo , Fármacos Neuroprotetores/farmacologia , Doença de Parkinson Secundária/metabolismo , Animais , Ansiedade/metabolismo , Ansiedade/patologia , Corpo Estriado/metabolismo , Depressão/metabolismo , Depressão/patologia , Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/patologia , Masculino , Camundongos , Oxidopamina , Doença de Parkinson Secundária/induzido quimicamente , Doença de Parkinson Secundária/patologiaRESUMO
Abnormalities in the thyroid hormones, like in hypothyroidism, are closely related to dementia and Alzheimer's disease demonstrating the main symptom of these disorders: memory deficit. In this study we evaluated the effect of chrysin on deficit spatial and aversive memories and the contribution of glutamatergic, cholinergic pathways and Na+, K+-ATPase activity on hippocampus and prefrontal cortex in hypothyroid adult female mice C57BL/6. Hypothyroidism was induced by the continuous exposure to 0.1% methimazole (MTZ) in drinking water for 31 days. The exposure to MTZ was associated to low plasma levels of thyroid hormones (TH) compared to the control group on the 32nd. Subsequently, euthyroid and MTZ-induced hypothyroid mice received (intragastrically) either vehicle or chrysin (20 mg/kg) once a day for 28 consecutive days. After treatments mice performed the following behavioral assessments: open-field test (OFT), morris water maze (MWM) and passive avoidance test. Additionally, plasma TH levels were measured again, as well as glutamate levels, Na+,K+-ATPase and acetylcholinesterase (AChE) activities were analyzed in the hippocampus and prefrontal cortex of mice. Mice with hypothyroidism showed a deficit of spatial and aversive memory and chrysin treatment reversed these deficits. It also reduced the levels of glutamate and decreased Na+,K+-ATPase activity in both cerebral structures in the hypothyroid mice compared with the euthyroid ones, with the exception of glutamate in the hippocampus, which was a partial reversal. AChE activity was not altered by treatments. Together, our results demonstrate that chrysin normalized hippocampal glutamate levels and Na+,K+-ATPase activity, which could be involved in the reversal of memory deficit.
Assuntos
Ácido Glutâmico , Hipotireoidismo , Animais , Feminino , Flavonoides , Hipocampo/metabolismo , Hipotireoidismo/induzido quimicamente , Hipotireoidismo/tratamento farmacológico , Camundongos , Camundongos Endogâmicos C57BL , ATPase Trocadora de Sódio-Potássio/metabolismoRESUMO
Background: ultraviolet radiation types A and B (UV) (400-315nm and 315-280nm respectively) are the main components present in sunlight known to cause skin injuries. Arnica montana is a plant that has been widely studied for containing anti-inflammatory, healing and analgesic properties capable of preventing or ameliorating lesions. Here, we investigated the therapeutic effect of topical application of Arnica montana after UVB-induced cutaneous injuries in mice.Methods: mice were exposed to UVB radiation (Philips TL40W/12 RS lamp) in a period of 3 hours. After one hour of radiation exposure, the animals were treated with topical application of Arnica montana ointment (250 mg/g) in the ear. At the time of 16 hours after treatment, the parameters of edema, oxidative stress and inflammatory reaction were measured in the ear of mice.Results: our results demonstrated that topical treatment with Arnica montana reduced the UVB-induced inflammatory response as demonstrated by the reduction of ear edema, inhibition of myeloperoxidase activation, decrease of nuclear factor kappa B levels and reduction of proinflammatory cytokines levels, such as interleukin-1beta, interleukin-6, tumour necrosis factor-alpha and interferon-gamma. In addition, Arnica montana ameliorated oxidative damage mediated by UVB radiation, as demonstrated by the reduction of lipid peroxidation, protein oxidation and increase of tissue antioxidant capacity and glutathione levels in the ear.Conclusion: we concluded that Arnica montana ointment is effective in alleviating the auricular inflammatory process and oxidative damage induced by acute UVB radiation, sustaining the traditional use of Arnica montana for the treatment of skin disorders.
Assuntos
Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Arnica , Edema/tratamento farmacológico , Transtornos de Fotossensibilidade/tratamento farmacológico , Preparações de Plantas/uso terapêutico , Lesões Experimentais por Radiação/tratamento farmacológico , Raios Ultravioleta/efeitos adversos , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Citocinas/metabolismo , Edema/metabolismo , Masculino , Camundongos , NF-kappa B/metabolismo , Pomadas , Estresse Oxidativo/efeitos dos fármacos , Peroxidase/metabolismo , Transtornos de Fotossensibilidade/metabolismo , Preparações de Plantas/farmacologia , Lesões Experimentais por Radiação/metabolismoRESUMO
This study aimed to evaluate the antimicrobial activity of 2-phenylethynyl-butyltellurium (PEBT) in Escherichia coli and the relation to its pro-oxidant effect. For this, we carried out disk diffusion test, minimum inhibitory concentration (MIC) assay, and survival curve analysis. We also measured the level of extracellular reactive oxygen species (ROS), activity of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), and level of non-protein thiols (NPSH). PEBT at 1.28 and 0.128 mg/disk exhibited antimicrobial capability in the disk diffusion test, with an MIC value of 1.92 mg/ml, whereas PEBT at 0.96, 1.92, and 3.84mg/ml inhibited bacterial growth after a 9-h exposure. PEBT at 3.84, 1.92, and 0.96 mg/ml increased extracellular ROS production, decreased the intracellular NPSH level, and reduced the SOD and CAT activities. Glutathione or ascorbic acid in the medium protected the bacterial cells from the antimicrobial effect of PEBT. In conclusion, PEBT exhibited antimicrobial activity against E. coli, involving the generation of ROS, oxidation of NPSH, and reduction of the antioxidant defenses in the bacterial cells.
Assuntos
Anti-Infecciosos/farmacologia , Escherichia coli/efeitos dos fármacos , Compostos Organometálicos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Antioxidantes/farmacologia , Ácido Ascórbico/metabolismo , Catalase/metabolismo , Escherichia coli/crescimento & desenvolvimento , Glutationa/metabolismo , Testes de Sensibilidade Microbiana , Compostos Organometálicos/química , Oxirredução , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , TelúrioRESUMO
This study has evaluated the action of flavonoid hesperidin on the neurotoxic effects caused by the intake of iron (Fe) in Drosophila melanogaster. Male adult flies, aged 1-3 days, have been divided into four groups of 50 each: (1) control, (2) Hsd 10 µM, (3) Fe 20 mM (4) Hsd 10 µM + Fe 20 mM. During the exposure protocol, the flies have been exposed to a diet containing Hsd and/or Fe for 48 h. The survival and behavioral analyses have been carried out in vivo, and ex vivo. The analyses involved acetylcholinesterase (AChE) activity and Fe levels in the flies' heads and bodies and determination of dopaminergic levels, cellular and mitochondrial viability, activities of superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), reactive species levels (RS), thiobarbituric acid reactive substances (TBARS) and contents of total thiols and non-proteic thiols (NPSH) in the flies' heads. A significant negative correlation between Fe levels in the head of the flies and the survival, dopamine levels and antioxidant enzymes in the head of the flies has been found. Additionally, significant positive correlation between Fe levels in the head of the flies with negative geotaxis RS and AChE activity in the head of the flies has been found. It demonstrates that the flies which had higher levels of Fe in their heads have demonstrated more susceptibility to neurotoxicity. An important result from our study is that Hsd treatment promotes a decrease in Fe concentration in the head, restores dopamine levels and cholinergic activity of the flies and improves motor function caused by Fe. Hsd also ameliorates Fe induced mortality, oxidative stress and mitochondrial dysfunction. Our results have demonstrated the neuroprotective effect of Hsd and it suggests that flavonoid acts in different ways to protect against the Parkinson disease caused by Fe exposure such as the direct scavenging of RS and activation of antioxidant enzymes.
Assuntos
Dopamina/metabolismo , Drosophila melanogaster/efeitos dos fármacos , Hesperidina/farmacologia , Ferro/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Doença de Parkinson Secundária/induzido quimicamente , Animais , Biomarcadores , Masculino , Metalotioneína/metabolismo , Mitocôndrias , Atividade Motora/efeitos dos fármacos , Oxirredução , Doença de Parkinson Secundária/prevenção & controleRESUMO
This study aims to investigate the protective effect of p-chloro-phenyl-selenoesterol [PCS; 0,2 mg/kg; 10 ml/kg i.g.) in colitis induced by 2,4,6-trinitrobenzene sulfonic acid [TNBS; 2 mg/100 µl 50% ethanol; intrarectally) in mice. Several parameters including weight, length, histological analyses determination, thiobarbituric acid reactive species, reactive species levels, superoxide dismutase, catalase, and myeloperoxidase (MPO) activity of colon were evaluated. The serum levels of tumor necrosis factor alpha [TNF-α) and interleukin 6 [IL-6) were also assessed. Treatment with PCS reduced the clinical and histopathologic severity of TNBS-induced colitis, characterized by colon length reduction and increased colon weight and microscopic intestinal inflammation. The therapeutic effects of PCS in this model were associated with significant decrease in proinflammatory cytokines TNF-α and IL-6 and decrease in MPO activity. Furthermore, combined with improvements in inflammatory parameters, treatment with the PCS was able to decrease oxidative stress and to prevent the decrease in antioxidant defenses in animals with TNBS-induced colitis. This finding suggests that PCS can improve experimental colitis in mice and it could be a potential therapeutic agent for the treatment of patients with IBD. J. Cell. Biochem. 118: 709-717, 2017. © 2016 Wiley Periodicals, Inc.