RESUMO
Memory consolidation is associated with the regulation of protein kinases, which impact synaptic functions and promote synaptogenesis. The administration of spermidine (SPD) has been shown to modulate major protein kinases associated with memory improvement, including the Ca2+-dependent protein kinase (PKC) and cAMP-dependent protein kinase (PKA), key players in the cAMP response element-binding protein (CREB) activation. Nevertheless, the initial mechanism underlying SPD-mediated memory consolidation remains unknown, as we hypothesize a potential involvement of the memory consolidation precursor, Ca2+/calmodulin-dependent protein kinase II-α (CaMKIIα), in this process. Based on this, our study aimed to investigate potential interactions among PKC, PKA, and CREB activation, mediated by CaMKIIα activation, in order to elucidate the SPD memory consolidation pathway. Our findings suggest that the post-training administration of the CaMKII inhibitor, KN-62 (0.25 nmol, intrahippocampal), prevented the memory enhancement induced by SPD (0.2 nmol, intrahippocampal) in the inhibitory avoidance task. Through western immunoblotting, we observed that phosphorylation of CaMKIIα in the hippocampus was facilitated 15 min after intrahippocampal SPD administration, resulting in the activation of PKA and CREB, 180 min after infusion, suggesting a possible sequential mechanism, since SPD with KN-62 infusion leads to a downregulation in CaMKIIα/PKA/CREB pathway. However, KN-62 does not alter the memory-facilitating effect of SPD on PKC, possibly demonstrating a parallel cascade in memory acquisition via PKA, without modulating CAMKIIα. These results suggest that memory enhancement induced by SPD administration involves crosstalk between CaMKIIα and PKA/CREB, with no PKC interaction.
Assuntos
Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico , Proteínas Quinases Dependentes de AMP Cíclico , Memória , Ratos Wistar , Transdução de Sinais , Espermidina , Animais , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Ratos , Espermidina/farmacologia , Masculino , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Memória/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Fosforilação/efeitos dos fármacos , Sulfonamidas/farmacologia , Benzilaminas/farmacologia , Benzilaminas/administração & dosagem , Aprendizagem da Esquiva/efeitos dos fármacos , Proteína Quinase C/metabolismo , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/análogos & derivadosRESUMO
The aim of this work was to evaluate the toxicological action of AH Plus (AHP), Bio-C Sealer (BCS), and EndoSequence BC Sealer (ESB), using Drosophila melanogaster as the model organism performing in vivo and ex vivo analysis. D. melanogaster were exposed for 10 days to three concentrations (5 mg/ml, 10 mg/ml, and 20 mg/ml) of AHP, BCS, and ESB sealers mixed with 10 ml of standard diet. During this period, the mortality of flies was evaluated. On the 11th day, the locomotor activity test was performed and the flies were euthanized for oxidative damage analysis (reactive species and lipid peroxidation) and cell viability (resazurin reduction). For the mortality curves evaluation, the log-rank test (Mantel-Cox) was used. For the analysis of other data, a one-way analysis of variance (ANOVA) was applied, followed by Tukey's post hoc test (α = 0.05). Regarding mortality, there were no significant differences. The locomotor activity was reduced, mainly in the two highest concentrations of AHP and BCS. Besides, reactive species generation was bigger in the AHP 20 mg/ml group. AHP induced a lipid peroxidation increase in all three concentrations tested, when compared to other sealers. Considering cell viability, the two highest concentrations of AHP reduced this parameter; while in other sealers, viability was reduced only in the highest concentration. AHP showed changes in oxidative markers that led to greater damage to the flies.
RESUMO
Elevated D-dimer levels at hospital admission may also indicate a higher likelihood of progressing to a severe or critical state. This study aimed to assess reactive oxygen species (ROS), non-enzymatic antioxidant reduced glutathione (GSH), and D-dimer levels in COVID-19 patients upon admission, examining their association with mortality outcomes. Data was collected from the medical records of 170 patients hospitalized in a referral hospital unit between March 2020 and December 2021. Patients were divided into two groups: the ward bed group (n = 87), comprising 51% with moderate clinical conditions, and the intensive care unit (ICU) group (n = 83), comprising 49% with severe conditions. The mean age was 59.4 years, with a male predominance of 52.4%. The overall death rate was 43%, with 30.6% in the moderate group and 69.4% in the severe group. The average time from symptom onset to hospitalization was 6.42 days. Results showed that non-survivors had high D-dimer and ROS counts, longer ICU stays, and worse saturation levels at admission. In conclusion, elevated ROS and D-dimer levels may contribute to worse outcomes in critically ill patients, potentially serving as specific and sensitive predictors of poor outcomes upon admission.
Assuntos
COVID-19 , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Espécies Reativas de Oxigênio , SARS-CoV-2 , Glutationa , Estresse OxidativoRESUMO
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
Sickness behavior is an expression of a central motivational state triggered by activation of the immune system, being considered a strategy of the organism to fight infection. Sickness behavior is induced by peripheral administration of lipopolysaccharide (LPS). LPS can increase the levels of proinflammatory cytokines, which induce the activation of the kynurenine pathway (KP) and behavioral alterations. Previous studies have shown that omega-3 (n-3) polyunsaturated fatty acid (PUFA) has anti-inflammatory properties. Because of this, the purpose of the present study was to evaluate the protective effect of fish oil (FO) supplementation against LPS-induced sickness behavior in aged mice with respect to anhedonia, locomotor activity and body weight. Moreover, we evaluated the ability of FO treatment on the regulation of neuroinflammation (levels of interleukin-1ß, interleukin-6, tumor factor necrosis-α and interferon-γ), KP biomarkers (levels of tryptophan, kynurenine, kynurenic acid, 3-hydroxykynurenine and quinolinic acid and activities of indoleamine-2,3-dioxygenase, kynurenine monooxygenase and kynurenine aminotransferase) and serotonergic system (levels of serotonin and 5-hydroxyindoleactic acid) in the hippocampus, striatum and prefrontal cortex of LPS-treated mice. We found that FO prevented the LPS-mediated body weight loss, anhedonic behavior, reduction of locomotor activity, up-regulation of the proinflammatory cytokines and serotoninergic alterations. We also found that FO was effective in modulating the KP biomarkers, inhibiting or attenuating KP dysregulation induced by LPS. Together, our results indicated that FO may have beneficial effects on LPS induced sickness-behavior in aged mice either by modulating central inflammation, KP and serotonergic signaling (indirectly effect) or by fatty acids incorporation into neuronal membranes (direct effect).
Assuntos
Envelhecimento/efeitos dos fármacos , Envelhecimento/fisiologia , Encéfalo/efeitos dos fármacos , Óleos de Peixe/farmacologia , Cinurenina/metabolismo , Anedonia/efeitos dos fármacos , Animais , Comportamento Animal/efeitos dos fármacos , Biomarcadores/metabolismo , Peso Corporal/efeitos dos fármacos , Encéfalo/metabolismo , Citocinas/metabolismo , Inflamação/metabolismo , Lipopolissacarídeos/toxicidade , Locomoção/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BLRESUMO
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
Monosodium glutamate (MSG) is the most widely used additive in the food industry; however, some adverse effects of this additive, including functional, learning, and behavioral alterations, have been observed in experimental animals and humans. Studies have shown learning and memory impairment in adult animals exposed to MSG. However, studies relating exposure to MSG to acetylcholinesterase (AChE) and Na+, K+-ATPase activities and memory damage are still scarce in the literature. The aim of the present study was to assess the possible protective effects of selenofuranoside, an organoselenium compound, against the impairment of long-term memory, Na+, K+-ATPase and AChE activities, and oxidative stress after MSG exposure in rats. MSG (2g/kg) and/or selenofuranoside (5mg/kg) were administered orally to 5-week-old male Wistar rats for 10days. On the 10th day, after the administration of last dose of the drug(s), the rats were subjected to behavioral tests: the open-field test and step-down passive avoidance task (SDPA). The blood, liver, kidney, cortex, and hippocampus were removed to determine the oxidative stress parameters, such as the levels of reactive species, lipid peroxidation, antioxidant enzyme activities, and endogenous nonenzymatic antioxidant content. Furthermore, the cortex and hippocampus were used to determine the Na+, K+-ATPase and AChE activities. The results demonstrate that the administration of MSG led to long-term memory impairment, as shown in the SDPA task, and also hippocampal and cortical Na+, K+-ATPase inhibition. There were no alterations in the AChE activity and oxidative stress parameters. Treatment with selenofuranoside attenuated memory impairment associated with MSG exposure by improving the hippocampal Na+, K+-ATPase activity.
Assuntos
Antioxidantes/uso terapêutico , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/tratamento farmacológico , Compostos Organosselênicos/uso terapêutico , Pentoses/uso terapêutico , Glutamato de Sódio/toxicidade , ATPase Trocadora de Sódio-Potássio/metabolismo , Acetilcolinesterase/metabolismo , Trifosfato de Adenosina/farmacologia , Análise de Variância , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Catalase/metabolismo , Colesterol/metabolismo , Modelos Animais de Doenças , Comportamento Exploratório/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
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.
Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Compostos Organosselênicos/farmacologia , Animais , Citocinas/biossíntese , Modelos Animais de Doenças , Feminino , Mediadores da Inflamação/metabolismo , Doenças Inflamatórias Intestinais/metabolismo , Doenças Inflamatórias Intestinais/patologia , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Peroxidase/metabolismo , Ácido Trinitrobenzenossulfônico/toxicidadeRESUMO
Herpes simplex viruses can cause uncommon systemic complications as acute liver failure (ALT) or urinary tract dysfunctions. Diphenyl diselenide, (PhSe)2 , a classical studied organic selenium compound, has a novel antiviral action against HSV-2 infection and well-known antioxidant and anti-inflammatory properties. This study aimed to investigate if (PhSe)2 reduces oxidative stress and systemic toxicity caused by HSV-2 infection in mice. Adult BALB/c mice were pre-treated with (PhSe)2 (5 mg kg-1 /day, intragastric, i.g.) during 5 days; at day 6 mice were infected with HSV-2 (10 µl-105 PFU/mL-1 ) and post-treated with (PhSe)2 for more 5 days. At day 11, they were killed and samples of liver and kidney were obtained to determine: reactive species (RS); malondialdehyde (MDA), and non-protein thiols (NPSH) levels; the activities of antioxidant enzymes, superoxide dismutase (SOD), and catalase (CAT). The activities of adenosine deaminase (ADA), Na+ /K+ -ATPase (liver and kidney); alanine aminotransferase (ALT), aspartate aminotransferase (AST), and the levels of urea (plasma) were determined as markers of hepatic and renal toxicity. The results revealed that (PhSe)2 treatment was effective against the increase of renal and hepatic oxidative stress in infected mice and also normalized hepatic and renal ADA activity. It recovered the activity of Na+ /K+ - and was not effective against the increase in urea levels in infected mice. Different from (PhSe)2 , acyclovir (positive control), caused an increase in ADA activity and a decrease in hepatic CAT activity. Considering the interest of alternative therapies to treat HSV-2 infections and secondary complications, (PhSe)2 become a notable candidate. J. Cell. Biochem. 118: 1028-1037, 2017. © 2016 Wiley Periodicals, Inc.
Assuntos
Antioxidantes/administração & dosagem , Antivirais/administração & dosagem , Derivados de Benzeno/administração & dosagem , Herpes Genital/tratamento farmacológico , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Compostos Organosselênicos/administração & dosagem , Adenosina Desaminase/metabolismo , Animais , Antioxidantes/efeitos adversos , Antioxidantes/farmacologia , Antivirais/efeitos adversos , Antivirais/farmacologia , Derivados de Benzeno/efeitos adversos , Derivados de Benzeno/farmacologia , Catalase/metabolismo , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Herpes Genital/virologia , Herpesvirus Humano 2/efeitos dos fármacos , Herpesvirus Humano 2/patogenicidade , Rim/metabolismo , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Compostos Organosselênicos/efeitos adversos , Compostos Organosselênicos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Superóxido Dismutase/metabolismoRESUMO
Alzheimer's disease (AD) is becoming more common due to the increase in life expectancy. This study evaluated the effect of selenofuranoside (Se) in an Alzheimer-like sporadic dementia animal model. Male mice were divided into 4 groups: control, Aß, Se, and Aß + Se. Single administration of Aß peptide (fragments 25-35; 3 nmol/3 µL) or distilled water was administered via intracerebroventricular (i.c.v.) injection. Selenofuranoside (5 mg/kg) or vehicle (canola oil) was administered orally 30 min before Aß and for 7 subsequent days. Memory was tested through the Morris water maze (MWM) and step-down passive-avoidance (SDPA) tests. Antioxidant defenses along with reactive species (RS) were assessed. Inflammatory cytokines levels and AChE activity were measured. SOD activity was inhibited in the Aß group whereas RS were increased. AChE activity, GSH, and IL-6 levels were increased in the Aß group. These changes were reflected in impaired cognition and memory loss, observed in both behavioral tests. Se compound was able to protect against memory loss in mice in both behavioral tests. SOD and AChE activities as well as RS and IL-6 levels were also protected by Se administration. Therefore, Se is promising for further studies.
Assuntos
Acetilcolinesterase/metabolismo , Doença de Alzheimer/patologia , Inflamação , Transtornos da Memória/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Compostos Organosselênicos/uso terapêutico , Estresse Oxidativo , Pentoses/uso terapêutico , Doença de Alzheimer/complicações , Peptídeos beta-Amiloides/toxicidade , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Glutationa/metabolismo , Glutationa Redutase/metabolismo , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/complicações , Camundongos , Estrutura Molecular , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Compostos Organosselênicos/química , Compostos Organosselênicos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Pentoses/química , Pentoses/farmacologia , Fragmentos de Peptídeos/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismoRESUMO
In this study, the effect of Chrysin (5,7-dihydroxyflavone), an important member of the flavonoid family, on memory impairment, oxidative stress and BDNF reduction generated by aging in mice were investigated. Young and aged mice were treated daily per 60days with Chrysin (1 and 10mg/kg; per oral, p.o.) or veichle (10ml/kg; p.o.). Mice were trained and tested in Morris Water Maze task. After the behavioural test, the levels of reactive species (RS), the activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), as well as the activity of Na(+), K(+)-ATPase and the levels of brain-derived neurotrophic factor (BDNF) were determined in the prefrontal cortex (PFC) and hippocampus (HC) of mice. Results demonstrated that the age-related memory decline was partially protected by Chrysin at a dose of 1mg/kg, and normalized at the dose of 10mg/kg (p<0.001). Treatment with Chrysin significantly attenuated the increase of RS levels and the inhibition of SOD, CAT and GPx activities of aged mice. Inhibition of Na(+), K(+)-ATPase activity in PFC and HP of aged mice was also attenuated by Chrysin treatment. Moreover, Chrysin marked mitigated the decrease of BDNF levels in the PFC and HC of aged mice. These results demonstrated that flavonoid Chrysin, an antioxidant compound, was able to prevent age-associated memory probably by their free radical scavenger action and modulation of BDNF production. Thus, this study indicates that Chrysin may represent a new pharmacological approach to alleviate the age-related declines during normal age, acting as an anti-aging agent.
Assuntos
Envelhecimento/psicologia , Fator Neurotrófico Derivado do Encéfalo/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Transtornos Cognitivos/prevenção & controle , Flavonoides/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Animais , Comportamento Animal/efeitos dos fármacos , Biomarcadores/metabolismo , Encéfalo/enzimologia , Encéfalo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Catalase/metabolismo , Glutationa Peroxidase/metabolismo , Masculino , Camundongos , Distribuição Aleatória , ATPase Trocadora de Sódio-Potássio/metabolismo , Superóxido Dismutase/metabolismoRESUMO
O consumo da alface (Lactuca sativa) pode ser um importante meio de transmissão de váriasdoenças parasitárias. Assim, o controle parasitológico constitui um grande desafio quando se verificaa inclusão cada vez mais frequente de hortaliças na dieta da população mundial. O objetivo destetrabalho foi avaliar a contaminação por parasitos de interesse em saúde pública em alfaces (L. sativa)comercializadas no município de Itaqui, RS. No processo de amostragem, foram selecionadossupermercados e produtores locais da cidade de Itaqui. Foram investigadas 60 amostras de alface (Lsativa) da variedade crespa, sendo 30 de produtores locais e 30 dos mercados locais, todas adquiridasaleatoriamente. As amostras de alface foram acondicionadas em sacos de polietileno limpos eidentificados. As folhas foram separadas uma a uma e lavadas em recipientes de vidro esterilizadoscom 250 mL de água destilada. A água resultante do processo de lavagem foi analisada utilizando-setrês técnicas parasitológicas: exame direto, sedimentação espontânea (Lutz) e centrífugo-flutuaçãoem sulfato de zinco a 33 por cento (Faust). Para a caracterização morfológica dos parasitos, utilizou-semicroscópio óptico. Das 60 amostras analisadas, 29 (48,3 por cento) apresentaram algum tipo de parasito,das quais 19 (63,3 por cento) eram procedentes de produtores locais e 10 (36,7 por cento), dos mercados locais.Foram encontrados ovos de Ascaris sp (5 por cento) e cistos de Giardia lamblia (38 por cento) e Entamoeba sp(13 por cento). A verificação da presença de parasitos, sobretudo helmintos e protozoários, especialmenteem hortaliças, é de grande interesse para a saúde pública, visto que fornece subsídios para o serviçode vigilância sanitária sobre o estado higiênico desses produtos.
The consumption of lettuce (Lactuca sativa) can be an important means of transmission of severalparasitic diseases, so the increasing inclusion of vegetables in the diet of the world populationpresents an important challenge. The objective of this study was to evaluate the contamination oflettuce (L. sativa) marketed in the municipality of Itaqui (RS) by parasites of interest to public health.A sampling process was used, selecting supermarkets and local producers in the city of Itaqui. Weinvestigated 60 samples of lettuce (L. sativa) of the curly variety, from 30 local producers and 30local markets, all acquired at random. The lettuce samples were placed in clean plastic bags andidentified. The leaves were separated and washed in a glass container with 250 ml of sterile distilledwater. The wash water was analyzed using three parasitological techniques: direct examination,spontaneous sedimentation technique (Lutz) and flotation of zinc sulfate to 33 percent (Faust). Themorphological features of the parasite were examined by means of an optical microscope. Of the60 samples analyzed, 29 (48.33 percent) had some type of parasites. Of these, 19 (63.34 percent) were fromlocal producers and 10 (36.66 percent) from local markets. Eggs were found of Ascaris sp. (5 percent) andcysts of Giardia lamblia (38 percent) and Entamoeba sp. (13 percent). Checking for the presence of parasites,particularly helminths and protozoa, especially in vegetables, has great interest for public health,because it supplements health surveillance on the hygienic condition of the goods.
Assuntos
Lactuca/parasitologia , Contaminação de Alimentos , Doenças Parasitárias , VerdurasRESUMO
Peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists not only improve metabolic abnormalities of diabetes and consequent diabetic nephropathy, but they also protect against non-diabetic kidney disease in experimental models. Here, we investigated the effect of PPAR-γ agonist pioglitazone against acute renal injury on a cisplatin model in mice. Nephrotoxicity was induced by a single intraperitoneal (i.p.) injection of cisplatin (10 mg kg(-1)). Pioglitazone was administered for six consecutive days in doses of 15 or 30 mg kg(-1) day(-1), per os (p.o.), starting 3 days before cisplatin injection. Cisplatin treatment to mice induced a marked renal failure, characterized by a significant increase in serum urea and creatinine levels and alterations in renal tissue architecture. Cisplatin exposure induced oxidative stress as indicated by decreased levels of non-enzymatic antioxidant defenses [glutathione (GSH) and ascorbic acid levels] and components of the enzymatic antioxidant defenses [superoxide dismutase (SOD), catalase (CAT) glutathione peroxidase (GPx), glutathione reductase (GR) and and glutathione S-transferase(GST) activities)] in renal tissue. Administration of pioglitazone markedly protected against the increase in urea and creatinine levels and histological alterations in kidney induced by cisplatin treatment. Pioglitazone administration ameliorated GSH and ascorbic acid levels decreased by cisplatin exposure in mice. Pioglitazone protected against the inhibition of CAT, SOD, GPx, GR and GST activities induced by cisplatin in the kidneys of mice. These results indicated that pioglitazone has a protective effect against cisplatin-induced renal damage in mice. The protection is mediated by preventing the decline of antioxidant status. The results have implications in use of PPAR-γ agonists in human application for protecting against drugs-induced nephrotoxicity.
Assuntos
Injúria Renal Aguda/tratamento farmacológico , Cisplatino/efeitos adversos , Rim/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Tiazolidinedionas/farmacologia , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/patologia , Animais , Ácido Ascórbico/sangue , Catalase/metabolismo , Creatinina/sangue , Glutationa/sangue , Glutationa Peroxidase/metabolismo , Injeções Intraperitoneais , Rim/patologia , Masculino , Camundongos , Estresse Oxidativo/efeitos dos fármacos , PPAR gama/agonistas , Pioglitazona , Superóxido Dismutase/metabolismoRESUMO
A growing body of evidence indicates that creatine (Cr) exerts beneficial effects on a variety of pathologies where energy metabolism and oxidative stress play an etiological role. However, the benefits of Cr treatment for epileptics are still shrouded in controversy. In the present study, we found that acute Cr treatment (300 mg/kg, p.o.) prevented the increase in electroencephalographic wave amplitude typically elicited by PTZ (30, 45 or 60 mg/kg, i.p.). Cr treatment also increased the latency periods of first myoclonic jerks, lengthened the latency periods of the generalized tonic-clonic seizures and reduced the time spent in the generalized tonic-clonic seizures induced by PTZ (60 mg/kg). Administration of PTZ (all doses) decreased Na(+), K(+)-ATPase activity as well as adenosine triphosphate (ATP) and adenosine diphosphate levels in the cerebral cortex, but Cr treatment prevented these effects. Cr administration also prevented increases in xanthine oxidase activity, adenosine monophosphate levels, adenosine levels, inosine levels and uric acid levels that normally occur after PTZ treatment (60 mg/kg, i.p.). We also showed that Cr treatment increased the total Cr (Cr + PCr) content, creatine kinase activity and the mitochondrial membrane potential (ΔΨ) in the cerebral cortex. In addition, Cr prevented PTZ-induced mitochondrial dysfunction characterized by decreasing ΔΨ, increasing thiobarbituric acid-reactive substance levels and increasing protein carbonylation. These experimental findings reinforce the idea that mitochondrial dysfunction plays a critical role in models of epileptic seizures and suggest that buffering brain energy levels through Cr treatment may be a promising therapeutic approach for the treatment of this neurological disease.
Assuntos
Creatina/administração & dosagem , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Convulsões/metabolismo , Convulsões/prevenção & controle , Animais , Humanos , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Estresse Oxidativo , Pentilenotetrazol/efeitos adversos , Carbonilação Proteica , Ratos , Ratos Wistar , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológicoRESUMO
It is known that selenium (Se) might play different roles in the progression of Alzheimer's disease (AD), but there is a lack of evidence that proves whether supplementation with Se is beneficial or not for the treatment of AD. Thus, the aim of the current study was to investigate the therapeutic effect of p,p'-methoxyl-diphenyl diselenide [(MeOPhSe)(2)], an organoselenium compound, against streptozotocin (STZ)-induced sporadic dementia of Alzheimer's type (SDAT) in rats. Male Wistar rats received STZ twice daily (1.0 mg/8 µl; 4 µl/ventricle) for 21 days. After 21 days of STZ injection, regular-diet-fed rats were supplemented with 10 ppm of (MeOPhSe)(2) during 30 days. At the end of this period, the rats were challenged in the Morris water maze and step-down passive avoidance tasks. The activity of acetylcholinesterase (AChE), deficit in cerebral energy metabolism (measurement of adenosine 5-triphosphate and adenosine 5-diphosphate levels), and oxidative and nitrosative stress were determined in the cortex and hippocampus of rats. The results demonstrated that (MeOPhSe)(2) dietary supplementation reverted STZ-induced memory impairment of rats in both cognitive tasks. The findings also indicated that (MeOPhSe)(2) dietary supplementation reverted oxidative stress in the STZ group (decreased reactive species and tyrosine nitration levels and enhanced nonprotein thiol levels). Moreover, (MeOPhSe)(2) dietary supplementation normalized AChE activity, which was enhanced by STZ injection, but did not revert the deficit in cerebral energy metabolism caused by STZ. The results of the present study indicated the therapeutic effect of the (MeOPhSe)(2)-supplemented diet in a rat model of SDAT.