RESUMO
Intracerebral haemorrhage (ICH) is a worldwide public health problem. Experimental studies have shown that oxidative stress plays an important role in the pathogenesis of ICH and could represent a target for its treatment. However, the blood-brain barrier is an obstacle to be overcome, as it hampers the administration of compounds to the central nervous system. In this study, we compared the effects of a quercetin-loaded nanoemulsion (QU-N) with the free form of the drug (QU-SP) in a collagenase-induced ICH rat model. Quercetin (QU) is a polyphenol that has an antioxidant effect in vitro, but due to its high lipophilicity, it has low bioavailability in vivo. In this study, animals submitted or not to ICH were treated with a single intraperitoneal QU dose (free or nanoemulsion) of 30 mg kg(-1). Motor assessment was evaluated by the open field, foot fault and beam walking behavioural tests. 72 h after surgery the haematoma size was evaluated and biochemical measurements were performed. Animals treated with QU-N had a significant improvement in the beam walking and open field tests. Also, QU-N was able to reduce the size of the haematoma, preserving the activity of glutathione S-transferase (GST), increasing GSH content, and the total antioxidant capacity. QU-SP recovered locomotor activity and increased the GSH content and the total antioxidant capacity. Thus, it can be observed that QU presented antioxidant activity in both formulations, but the incorporation into nanoemulsions increased its antioxidant effect, which was reflected in the improvement of the motor skills and in the haematoma size decrement. These results suggest that the nanoemulsion containing QU developed in this study could be promising for future studies on treatments for ICH.
Assuntos
Antioxidantes/administração & dosagem , Hemorragia Cerebral/tratamento farmacológico , Portadores de Fármacos/química , Nanoestruturas/química , Quercetina/química , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Peso Corporal/efeitos dos fármacos , Hemorragia Cerebral/etiologia , Cromatografia Líquida de Alta Pressão , Colagenases/metabolismo , Modelos Animais de Doenças , Emulsões/química , Glutationa/metabolismo , Glutationa Transferase/metabolismo , Locomoção/efeitos dos fármacos , Tamanho da Partícula , Quercetina/administração & dosagem , Quercetina/farmacologia , Ratos , Ratos WistarRESUMO
Adenosine triphosphate (ATP) plays a role in cell signaling. It was soon proposed that ATP activates ionotropic P2X receptors, exerting an influence on neurons as well as on glial cells. In addition to the fact that the activation of P2X and P2Y receptors can stimulate or inhibit the release of glutamate from rat hippocampal neurons, the release of ATP has been implicated in hippocampal long-term potentiation (LTP). Through different behavioral paradigms, this study aimed to investigate the participation of P2X7R in genetically modified (knockout (KO)) mice with the suppressed expression of this receptor and in the pharmacological blockage of this receptor in rats, as well as to evaluate the effect of environmental enrichment on potential mnemonic deficits. The results suggest that P2X7R participates in aversive memory processes: pharmacological blockage with the selective P2X7R antagonist, A-740003, in different time frames elicited dose-dependent impairments in memory acquisition, consolidation and retrieval in rats that were submitted to the contextual fear-conditioning (FC) task, and the deletion of P2X7R hampered the aversive memory processes of mice that were subjected to the FC paradigm. Experiments using mice that were subjected to environmental enrichment suggest that this form of stimulation reverses mnemonic impairments that are ascribed to the absence of the P2X7R, suggesting that these receptors do not participate on such a reversal. Finally, no alterations were observed in the habituation memory of P2X7KO mice.
Assuntos
Acetamidas/farmacologia , Memória/efeitos dos fármacos , Memória/fisiologia , Antagonistas do Receptor Purinérgico P2X/farmacologia , Quinolinas/farmacologia , Receptores Purinérgicos P2X7/fisiologia , Animais , Região CA1 Hipocampal/efeitos dos fármacos , Região CA1 Hipocampal/fisiologia , Condicionamento Psicológico/efeitos dos fármacos , Condicionamento Psicológico/fisiologia , Relação Dose-Resposta a Droga , Meio Ambiente , Medo/efeitos dos fármacos , Medo/fisiologia , Habituação Psicofisiológica/efeitos dos fármacos , Habituação Psicofisiológica/fisiologia , Abrigo para Animais , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Limiar da Dor/efeitos dos fármacos , Limiar da Dor/fisiologia , Distribuição Aleatória , Ratos Wistar , Receptores Purinérgicos P2X7/genéticaRESUMO
The present work evaluated the effects of nicotine (NIC), cotinine (COT), mecamylamine (MEC), methyllycaconitine (MLA) and dihydro-beta-eritroidine (DHßE) on memory extinction and the following biochemical parameters of the hippocampus: lipid peroxidation (LPO), antioxidant capacity (AC) and the phosphorylation of Extracellular-Signal-Regulated Kinase (ERK 1/2). Young male rats that were implanted bilaterally with cannulae were submitted to memory extinction tests sessions, and their hippocampi were dissected for biochemical assays. The extinction of fear memory was significantly improved by both nicotine and its metabolite. Cotinine significantly increased LPO, while nicotine significantly decreased it. Antioxidant capacity was increased by all treatments. Our results showed that cotinine, unlike nicotine, may increase oxidative stress in the hippocampus, but this increase depends upon the dose used and happens without causing corresponding impairments in cognitive function. Cotinine also increased the phosphorylation of ERK 1/2 in a similar fashion as nicotine. Considering these results, it is plausible to wonder to what extent nicotine-attributed effects are really due to the actions of this alkaloid and whether they could be due instead to cotinine or to cotinine-nicotine interactions within the brain.
Assuntos
Cotinina/farmacologia , Extinção Psicológica/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Memória/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Agonistas Nicotínicos/farmacologia , Nootrópicos/farmacologia , Animais , Antioxidantes/metabolismo , Comportamento Animal/efeitos dos fármacos , Cotinina/administração & dosagem , Cotinina/efeitos adversos , Cotinina/antagonistas & inibidores , Relação Dose-Resposta a Droga , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Hipocampo/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Neurônios/metabolismo , Nicotina/efeitos adversos , Nicotina/antagonistas & inibidores , Nicotina/farmacologia , Agonistas Nicotínicos/administração & dosagem , Agonistas Nicotínicos/efeitos adversos , Agonistas Nicotínicos/química , Antagonistas Nicotínicos/farmacologia , Nootrópicos/administração & dosagem , Nootrópicos/efeitos adversos , Nootrópicos/antagonistas & inibidores , Fosforilação/efeitos dos fármacos , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Ratos , Ratos WistarRESUMO
Psychotria is a complex genus whose neotropical species are known by the presence of glucosidic monoterpene indole alkaloids. These compounds are able to display a large range of effects on the central nervous system, such as anxiolytic, antidepressant, analgesic, and impairment of learning and memory acquisition. The aims of this study were to investigate the effects displayed by strictosidinic acid, isolated from Psychotria myriantha Mull. Arg. (Rubiaceae) leaves, on monoamine levels in rat hippocampus and on monoamine oxidase activity. A significance (p<0.01) of 83.5% reduction in 5-HT levels was observed after intra-hippocampal injection (20 µg/µl). After treatment by intraperitoneal route (10 mg/kg), a 63.4% reduction in 5-HT levels and a 67.4% reduction in DOPAC values were observed. The results indicate that strictosidinic acid seems to act on 5-HT system in rat hippocampus, possibly inhibiting precursor enzymes of 5-HT biosynthesis. The decrease verified in DOPAC levels suggests a role of strictosidinic acid in the dopaminergic transmission, probably due to an inhibition of monoamine oxidase activity, confirmed by the enzymatic assay, which demonstrated an inhibitory effect on MAO A in rat brain mitochondria.
Assuntos
Ácido 3,4-Di-Hidroxifenilacético/metabolismo , Carbolinas/farmacologia , Glicosídeos/farmacologia , Hipocampo/metabolismo , Monoaminoxidase/metabolismo , Extratos Vegetais/farmacologia , Psychotria/química , Serotonina/metabolismo , Animais , Carbolinas/administração & dosagem , Carbolinas/isolamento & purificação , Glicosídeos/administração & dosagem , Glicosídeos/isolamento & purificação , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Inibidores da Monoaminoxidase/administração & dosagem , Inibidores da Monoaminoxidase/isolamento & purificação , Inibidores da Monoaminoxidase/farmacologia , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Folhas de Planta , Ratos , Ratos Wistar , Serotonina/biossíntese , Antagonistas da Serotonina/administração & dosagem , Antagonistas da Serotonina/isolamento & purificação , Antagonistas da Serotonina/farmacologiaRESUMO
This study analyzed water quality in regions around Patos lagoon (Southern Brazil) that are under anthropogenic pressure. Water samples were collected from five different sites, including one used as a source for human consumption (COR) and others known to be influenced by human activities (IP). Danio rerio (Teleostei, Cyprinidae) organisms were exposed for 24h to these water samples, plus a control group. It was observed that: (1) reactive oxygen species levels were lower in COR and IP than in the control group; (2) glutamate-cysteine ligase (catalytic subunit) expression was higher in COR than in other sites; (3) exposure to all water samples affected long-term memory (LTM) when compared to control group. Thus, some water samples possess the ability to modulate the antioxidant system and to induce a decline in cognitive functions, as measured by LTM. The obtained results indicate that a combination of variables of different organization level (molecular, biochemical and behavioral) can be employed to analyze water quality in impacted regions.
Assuntos
Monitoramento Ambiental/métodos , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/fisiologia , Animais , Biomarcadores/metabolismo , Água Doce/química , Brânquias/efeitos dos fármacos , Brânquias/metabolismo , Glutamato-Cisteína Ligase/metabolismo , Glutationa/metabolismo , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Poluentes Químicos da Água/análise , Abastecimento de Água/análise , Peixe-Zebra/metabolismoRESUMO
Silymarin (SM), the active complex of milk thistle, is a lipophilic fruit extract and is composed of several isomer flavonolignans. Flavonoids are antioxidants found molecules capable of intercepting reactive oxygen species (ROS). The oxidative stress (OS) is caused by imbalance between antioxidant defenses and production of ROS causing oxidative damage to macromolecules. Brain is susceptible to oxidative stress and it is associated with age-related brain dysfunction. This study evaluated the effect of SM on biochemical parameters that evaluate OS in aged and young rat brain. For measures of OS were used measures of total oxyradical scavenging capacity (ACAP) through the concentration of ROS by fluorescence, lipid peroxidation (LPO), via FOX and TBARS, proteins oxidation by Western blot (WB). Rats were treated with SM at doses of 200 and 400mg/kg/day (SM200 and SM400). The LPO analyzed through FOX was increased in the hippocampus of aged animals treated with SM400, but in the cortex of young and aged, the highest dose of SM decreased LPO analyzed through TBARS. Both doses have seemed most effective in the reduction of oxidized proteins in aged brain. These results suggest that SM may contribute to the prevention of aged-related and pathological degenerative processes in the brain.
Assuntos
Antioxidantes/farmacologia , Encéfalo/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Silimarina/farmacologia , Fatores Etários , Animais , Encéfalo/metabolismo , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Oxirredução , Peróxidos/metabolismo , Proteínas/química , Proteínas/metabolismo , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/análiseRESUMO
Estrogen compounds have been described as important brain protectors. This study investigated the effects of estradiol valerate (EV--0.3 mg/kg) and two concentrations of tibolone (TB1=0.5 mg/kg and TB2=1 mg/kg) on brain oxidative stress parameters and blood biochemistry in ovariectomized female rats, of three different age groups (young--2 months, adult--8 months, and old--20 months). In the brain cortex, young and old TB2-treated and old no-hormone-replacement (NR) females showed lower lipid hydroperoxide (LPO) levels compared to young Sham and adult TB1 animals (P<0.05). Also in the cortex, both tibolone doses produced higher (P<0.05) total antioxidant capacity (TOSC) levels compared to EV-treated adult females. Ovariectomized adult females (NR, EV, TB1 and TB2) showed lower (P<0.05) TOSC levels in the hippocampus compared to the Sham control. Reactive oxygen species (ROS) were higher (P<0.05) in old females compared to all younger ones. TB2-treated adults showed higher plasma glucose (P<0.05) levels compared to old animals. Regardless of age, TB2 treatment increased female (P<0.05) LDL levels compared to Sham and EV-treated animals. In old females, TB2 significantly increased HDL levels compared to Sham controls, and decreased triglyceride levels were shown in EV, TB1 and TB2 compared to Sham old females. The Atherogenic Index of Plasma was higher (P<0.05) in adult tibolone-treated females compared to both young and old TB2-treated females. These results suggest that the effects of gonad steroid on brain and blood physiology change significantly with aging, and that evaluating hormonal treatment types and doses could be the key factor in the potential use of a specific hormone therapy.
Assuntos
Envelhecimento/fisiologia , Sangue/metabolismo , Encéfalo , Estradiol/análogos & derivados , Norpregnenos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Anticoncepcionais/farmacologia , Estradiol/farmacologia , Moduladores de Receptor Estrogênico/farmacologia , Feminino , Sequestradores de Radicais Livres/metabolismo , Peroxidação de Lipídeos , Fármacos Neuroprotetores/farmacologia , Ovariectomia , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismoRESUMO
Nicotine is the main alkaloid of tobacco and possesses well-established stimulant effects. Previous reports show that nicotine at low doses improves memory functions, while high doses impair memory. This study aims to analyze the effects of nicotine (NIC) on inhibitory avoidance task and on DNA damage, reactive oxygen species (ROS) concentration, total antioxidant capacity, and lipid peroxidation in cortex and hippocampus of old rats. Male Wistar rats of 24-26 months old (620-700g) were exposed i.p. to two doses (0.3 and 1mg/kg) of NIC daily during 9 days. The treatment NIC 0.3 enhanced long-term memory (p<0.05), whereas NIC 1 improved both short and long-term memories (p<0.05). DNA damage was observed only in hippocampus (p<0.05) after NIC 1 exposure. A similar result was obtained for ROS: higher levels were detected at NIC 1 treatment in hippocampus (p<0.05). No alterations in the total antioxidant capacity were verified after NIC exposure (0.3 and 1mg/kg) in both tissues (p>0.05). Finally, evidence of oxidative damage was observed in terms of lipid peroxides levels, being higher at NIC 1 in hippocampus (p<0.05). Overall the results indicate that deleterious effects paralleled the improved short and long-term memories at the highest NIC dose, since augmented DNA damage, ROS concentration and lipid peroxides levels were registered.
Assuntos
Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/crescimento & desenvolvimento , Hipocampo/efeitos dos fármacos , Hipocampo/crescimento & desenvolvimento , Nicotina/farmacologia , Nicotina/toxicidade , Agonistas Nicotínicos/farmacologia , Agonistas Nicotínicos/toxicidade , Animais , Antioxidantes/metabolismo , Aprendizagem da Esquiva/efeitos dos fármacos , Ensaio Cometa , Dano ao DNA/efeitos dos fármacos , Sequestradores de Radicais Livres/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Peróxidos Lipídicos/metabolismo , Memória/efeitos dos fármacos , Memória de Curto Prazo/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismoRESUMO
This study investigated the effects of estradiol valerate (EV) and tibolone (TB) treatments on some memory parameters of ovariectomized young (2 months), adult (8 months) and old (20 months) female rats. A Sham-operated group was used as control and the animals were treated daily, by oral gavage, with saline (Sham and placebo NR group), EV (0.3 mg/kg) or TB (0.5 or 1 mg/kg, TB1 and TB2, respectively). In step-down inhibitory avoidance task, the latency of old TB2-treated females in the short-term test was significantly inferior (p<0.05), compared to TB2 adults. In the elevated plus maze, adult NR females spent significantly less time (p<0.05) in the open arms as compared with EV and TB2-treated animals. Additionally, adult TB2-treated females spent significantly less time in the closed arms compared to Sham, NR and TB1 groups. Finally, in the water maze retention test, young TB1-treated animals performed worse when compared to Sham, EV and TB2 females. In the old animals, EV treatment hampered subject performance as compared to all other treatments. Taken together, these results indicate that ovarian hormones differently affect female memory in an age-dependent manner.
Assuntos
Antagonistas de Androgênios/farmacologia , Estradiol/análogos & derivados , Estrogênios/farmacologia , Memória/efeitos dos fármacos , Norpregnenos/uso terapêutico , Progestinas/farmacologia , Envelhecimento , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Aprendizagem da Esquiva/fisiologia , Estradiol/administração & dosagem , Estradiol/farmacologia , Feminino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Memória/fisiologia , Norpregnenos/administração & dosagem , Ovariectomia , Ratos , Ratos WistarRESUMO
Microcystins produced by cyanobacteria are potent inhibitors of some protein phosphatases, but recent evidence also indicates its potential to generate oxidative stress. In the present study, the effects of microcystin raw extracts (Mic; 0.01 and 20microg/L) and purified okadaic acid (OA; 0.01 and 10microg/L) on short- and long-term memory alteration and antioxidant and oxidative damage were investigated in hippocampus of rats. The results showed an amnesic effect with 0.01 and 20microg/L Mic on retrieval and only with 0.01microg/L Mic on spatial learning. Parallel to these effects oxidative damage was observed as evidenced by augmented levels of lipid peroxides and DNA damage and the absence of antioxidant responses in terms of total oxyradical scavenging capacity. Phase II reactions catalyzed by glutathione-S-transferase were not modified after microcystins exposure. Overall this study showed physiological events (retrieval and spatial learning) that can be related to the classical toxic effects of microcystins (i.e., phosphatase inhibition). In addition, evidence of alternative toxicity mechanisms via oxidative stress generation was also obtained. The fact that organic anion transporter polypeptides (OATP) involved in microcystins uptake are expressed not only in liver but also in brain points to the environmental relevance of the observed effects.