RESUMO
There are many studies that have sought to find drug therapies to prevent harm arising from sepsis. Such studies have represented a progress in the support to septic patients and also in the development of new pharmacological alternatives. Our interest was to investigate the caffeine effect on sepsis behavioural and memory impairments. Male rats were anaesthetized and the surgery was made to allow exposure of the caecum, which was then squeezed to extrude a small amount of faeces from the perforation site, which was later placed back into the peritoneal cavity. This procedure, which served to generate experimental sepsis, is herein referred to as ceccum ligation and perforation (CLP). The caffeine (10 mg/kg) was administered by gavage route, once daily, during 7 or 14 consecutive days to investigate the effects of acute or subchronic caffeine treatment on long-term behavioural and cognitive deficits induced by CLP. On the last day, 1 hr after caffeine administration, the animals were submitted to open-field, elevated plus maze (EPM), forced swimming and step-down inhibitory avoidance tests. The results showed that caffeine increased the percentage of open arm entries and open arm time in the EPM test, and reduced the immobility time when compared to the sham-operated group. The caffeine also increased the latency in the inhibitory avoidance test platform. Our results demonstrated that the caffeine improved behavioural changes and improved the neurocognitive deficits of sepsis-surviving animals. It is possible that blockage of the adenosine receptors may be responsible for the results here observed.
Assuntos
Comportamento Animal/efeitos dos fármacos , Cafeína/farmacologia , Transtornos Cognitivos/prevenção & controle , Cognição/efeitos dos fármacos , Antagonistas de Receptores Purinérgicos P1/farmacologia , Sepse/tratamento farmacológico , Animais , Transtornos Cognitivos/microbiologia , Transtornos Cognitivos/psicologia , Modelos Animais de Doenças , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Ratos Wistar , Tempo de Reação/efeitos dos fármacos , Sepse/complicações , Sepse/microbiologia , Sepse/psicologia , Fatores de TempoRESUMO
Sepsis and its complications are important causes of mortality in intensive care units and sepsis survivors may present long-term cognitive and emotional impairments, including memory deficits and anxiety symptoms. In the present study, we investigated whether repeated nicotine administration can affect the behavioral changes in sepsis-surviving rats. Male Wistar rats were divided in two groups: sham-operated and experimental sepsis induced by cecal ligation and puncture (CLP). The animals were injected subcutaneously with nicotine (0.1 mg/kg) or vehicle once a day during 1 week before and/or 1 week after sepsis induction. Thirty minutes after the last administration (i.e., 7 days after surgery), the animals were tested in the open field, elevated plus-maze and step-down inhibitory avoidance tasks. The repeated nicotine treatment did not affect the survival rate in the sepsis group (50%). Moreover, no significant changes on locomotor activity were observed in the sepsis group while the treatment with nicotine during 1 week after surgery reduced the locomotion of sepsis-surviving rats in the open field. It is important to note that both schedules of nicotine treatment (prior and/or after CLP) improved the sepsis-induced anxiogenic-like responses. Interestingly, nicotine was able to improve short- and long-term inhibitory avoidance memory impairments, observed in sepsis survivors, only when administered during 2 consecutive weeks (i.e., prior and after CLP). Taken together, these results indicate that repeated nicotine administration does not alter the survival rate in rats submitted to CLP and provide new evidence that nicotine can improve long-lasting memory impairments and anxiogenic-like responses in sepsis-surviving animals.
Assuntos
Ansiedade/tratamento farmacológico , Transtornos da Memória/tratamento farmacológico , Nicotina/uso terapêutico , Agonistas Nicotínicos/uso terapêutico , Sepse/complicações , Animais , Ansiedade/complicações , Aprendizagem da Esquiva/efeitos dos fármacos , Locomoção/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/complicações , Ratos , Ratos WistarRESUMO
Previous studies from our group have indicated important biological properties of the ethanolic extract and isolated compounds from the bulbs of Cipura paludosa (Iridaceae), a native plant widely distributed in northern Brazil, including antioxidant, neuroprotective and anti-nociceptive activities. In the present study, the effects of the ethanolic extract and its two naphthoquinones (eleutherine and isoeleutherine) on the short- and long-term memory of adult rodents were assessed in social recognition and inhibitory avoidance tasks. Acute pre-training oral administration of the ethanolic extract improved the short-term social memory in rats as well as facilitated the step-down inhibitory avoidance short- and long-term memory in mice. Moreover, the co-administration of 'non-effective' doses of the extract of Cipura paludosa and the adenosine receptor antagonists caffeine (non-selective), DPCPX (adenosine A1 receptor antagonist) and ZM241385 (adenosine A2A receptor antagonist) improved the social recognition memory of rats. In the inhibitory avoidance task, the co-administration of sub-effective doses of the extract with caffeine or ZM241385, but not with DPCPX, improved the short- and long-term memory of mice. Finally, the acute oral administration of eleutherine and isoeleutherine facilitated the inhibitory avoidance short- and long-term memory in mice. These results demonstrate for the first time the cognitive-enhancing properties of the extract and isolated compounds from the bulbs of Cipura paludosa in rodents and suggest a possible involvement of adenosine A1 and A2A receptors in these effects.
Assuntos
Memória de Longo Prazo/efeitos dos fármacos , Memória de Curto Prazo/efeitos dos fármacos , Naftoquinonas/farmacologia , Extratos Vegetais/farmacologia , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Brasil , Cafeína/farmacologia , Etanol/química , Furanos/isolamento & purificação , Furanos/farmacologia , Iridaceae/química , Masculino , Camundongos , Naftoquinonas/isolamento & purificação , Raízes de Plantas , Antagonistas de Receptores Purinérgicos P1/farmacologia , Ratos , Ratos Wistar , Receptor A1 de Adenosina/efeitos dos fármacos , Receptor A1 de Adenosina/metabolismo , Receptores A2 de Adenosina/efeitos dos fármacos , Receptores A2 de Adenosina/metabolismo , Triazinas/farmacologia , Triazóis/farmacologia , Xantinas/farmacologiaRESUMO
Previous studies from our group have indicated important biological properties of the ethanolic extract (EE) and isolated compounds from the bulbs of Cipura paludosa (Iridaceae), a native plant widely distributed in northern Brazil. In the present study, the effects of chronic treatment with the EE on the memory of adult rats exposed to methylmercury (MeHg) during early development were assessed. Pregnant rats were treated by gavage with a single dose of MeHg (8 mg/kg) on gestational day 15, the developmental stage critical for cortical neuron proliferation. Adult offspring were administered orally with the EE of C. paludosa (1, 10 or 100mg/kg) over 14 consecutive days. EE improved short-term social memory in a specific manner and facilitated the step-down inhibitory avoidance of short- and long-term memory. MeHg exposure induced pronounced long-lasting impairments in social recognition memory that were improved by EE. Moreover, EE significantly increased the step-down latencies specifically during the short-term session in prenatal MeHg-exposed rats. These results demonstrate that EE reduced the long-lasting short-term learning and memory deficits induced by MeHg exposure. These findings may encourage further studies evaluating the cognitive enhancing properties of C. paludosa and its components on neuropathological conditions associated with exposure to environmental contaminants.
Assuntos
Iridaceae/química , Aprendizagem/efeitos dos fármacos , Transtornos da Memória/tratamento farmacológico , Memória de Longo Prazo/efeitos dos fármacos , Memória de Curto Prazo/efeitos dos fármacos , Compostos de Metilmercúrio/toxicidade , Extratos Vegetais/toxicidade , Animais , Etanol/farmacologia , Feminino , Aprendizagem/fisiologia , Masculino , Transtornos da Memória/induzido quimicamente , Memória de Longo Prazo/fisiologia , Memória de Curto Prazo/fisiologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/tratamento farmacológico , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Ratos , Ratos WistarRESUMO
OBJECTIVE: To analyse the behavioral effects of Melissa officinalis extract in rats following acute or subacute treatment. MATERIALS AND METHODS: The behavioral effects of an acute or subacute (10-day course) orally administered M. officinalis (MO; 0, 30, 100 or 300 mg/kg) ethanol extract were evaluated in male and female Wistar rats in elevated plus-maze (EPM), forced swimming (FS) and open field (OF) tests. The effects of diazepam (DZP; 1 mg/kg) and fluoxetine (FXT; 10 mg/kg) were also assessed. RESULTS: In the EPM test, the percentage of open arm entries and open arm times of both males and females given the subacute M. officinalis ethanol extract were significantly higher than those of the vehicle-treated animals but were at levels similar to those observed in the DZP group, regardless of the treatment length. In the FS test, immobility duration was significantly lower in both males and females treated with the plant extract when compared to vehicle-treated counterparts. A 10-day treatment with FXT induced the same antidepressant response, regardless of gender, and was more effective than the M. officinalis extract. Male and female rats demonstrated distinct gender profiles, and treatment × gender interactions were observed. Locomotion in the EPM and OF tests was not significantly altered by treatments. CONCLUSION: The potential psychoactive properties of M. officinalis may provide a unique pharmacological alternative for certain psychiatric disorders; however, the efficacy appears to be dependent on both gender and administration length.
RESUMO
Cipura paludosa (Iridaceae) is a plant that is distributed in the north region of Brazil. Its bulbs are used in folk medicine to treat inflammation and pain. Four naphthalene derivatives have been isolated from the bulbs of this plant. Three of them have been identified as the known naphthalene derivatives, eleutherine, iso-eleutherine, and hongkonin. The structure of the fourth and new component was determined as 11-hydroxyeleutherine by extensive NMR study. In addition, the IN VIVO effect of the two major compounds, eleutherine and iso-eleutherine, was evaluated in carrageenan-induced hypernociception and inflammation in mice. Eleutherine and iso-eleutherine (1.04-34.92 µmol/kg), dosed intraperitoneally (i.p.) or orally (p.o.), decreased the carrageenan-induced paw oedema (i.p. - inhibitions of 36 ± 7 % and 58 ± 14 %, respectively; p.o. - inhibitions of 36 ± 7 % and 58 ± 14 %, respectively). Iso-eleutherine, but not eleutherine, significantly reduced (inhibitions of 39 ± 4 %) the plasma extravasation induced by intradermal (i.d.) injection of carrageenan. Likewise, eleutherine and iso-eleutherine (1.04-34.92 µmol/kg, i.p. or p.o.) were also effective in preventing the carrageenan-induced hypernociceptive response (i.p. - inhibition of 59 ± 4 % and 63 ± 1 %, respectively; p.o. - inhibitions of 36 ± 7 % and 58 ± 14 %, respectively). It was also suggested that the anti-inflammatory and anti-hypernociceptive effects of eleutherine or iso-eleutherine partly depend on the interference with the synthesis or activity of mast cell products, kinins, cytokine, chemokines, prostanoids, or sympathetic amines. Our findings show that two major compounds of C. paludosa contain pharmacologically active constituents that possess antinociceptive and anti-inflammatory activity, justifying, at least in part, its popular therapeutic use for treating conditions associated with pain.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Iridaceae/química , Naftoquinonas/química , Naftoquinonas/farmacologia , Administração Oral , Animais , Anti-Inflamatórios não Esteroides/química , Brasil , Carragenina/toxicidade , Avaliação Pré-Clínica de Medicamentos , Edema/tratamento farmacológico , Feminino , Inflamação , Injeções Intraperitoneais , Espectroscopia de Ressonância Magnética , Masculino , Camundongos , Estrutura Molecular , Naftoquinonas/administração & dosagem , Naftoquinonas/isolamento & purificação , Dor/tratamento farmacológico , Raízes de Plantas/química , Plantas Medicinais/químicaRESUMO
In the present study, we evaluated the effects of the ethanolic extract (EE) of Cipura paludosa on locomotor, and anxiety- and depression-like behaviors of adult rats exposed to MeHg during early development. Additionally, the antioxidant enzymes catalase (CAT) and selenium-glutathione peroxidase (Se-GPx) were measured in cortical, hippocampal, and cerebellar tissues. Pregnant Wistar rats were treated by gavage with a single dose of MeHg (8 mg/kg) on gestational day 15, the developmental stage critical for cortical neuron proliferation. Moreover, prenatal MeHg exposure inhibited CAT and Se-GPx in the cortex and cerebellum. Chronic treatment with the EE of C. paludosa attenuated these emotional and antioxidant deficits induced by prenatal MeHg toxic exposure. This study provides novel evidence that developmental exposure to MeHg can affect not only cognitive functions but also locomotor, and anxiety- and depression-like behaviors.
Assuntos
Comportamento Animal/efeitos dos fármacos , Iridaceae/química , Compostos de Metilmercúrio/toxicidade , Organogênese/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Efeitos Tardios da Exposição Pré-Natal/prevenção & controle , Poluentes Químicos da Água/toxicidade , Animais , Catalase/metabolismo , Feminino , Glutationa Peroxidase/metabolismo , Masculino , Exposição Materna/efeitos adversos , Aprendizagem em Labirinto/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Extratos Vegetais/isolamento & purificação , Raízes de Plantas/química , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/enzimologia , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Ratos , Ratos Wistar , NataçãoRESUMO
The present study examined the antinociceptive effect of the ethanolic extract from Melissa officinalis L. and of the rosmarinic acid in chemical behavioral models of nociception and investigates some of the mechanisms underlying this effect. The extract (3-1000 mg/kg), given orally (p.o.) 1 h prior to testing, produced dose-dependent inhibition of acetic acid-induced visceral pain, with ID50 value of 241.9 mg/kg. In the formalin test, the extract (30-1000 mg/kg, p.o.) also caused significant inhibition of both, the early (neurogenic pain) and the late (inflammatory pain), phases of formalin-induced licking. The extract (10-1000 mg/kg, p.o.) also caused significant and dose-dependent inhibition of glutamate-induced pain, with ID50 value of 198.5 mg/kg. Furthermore, the rosmarinic acid (0.3-3 mg/kg), given p.o. 1 h prior, produced dose-related inhibition of glutamate-induced pain, with ID50 value of 2.64 mg/kg. The antinociception caused by the extract (100 mg/kg, p.o.) in the glutamate test was significantly attenuated by intraperitoneal (i.p.) treatment of mice with atropine (1 mg/kg), mecamylamine (2 mg/kg) or l-arginine (40 mg/kg). In contrast, the extract (100 mg/kg, p.o.) antinociception was not affected by i.p. treatment with naloxone (1 mg/kg) or D-arginine (40 mg/kg). It was also not associated with non-specific effects, such as muscle relaxation or sedation. Collectively, the present results suggest that the extract produced dose-related antinociception in several models of chemical pain through mechanisms that involved cholinergic systems (i.e. through muscarinic and nicotinic acetylcholine receptors) and the L-arginine-nitric oxide pathway. In addition, the rosmarinic acid contained in this plant appears to contribute for the antinociceptive property of the extract. Moreover, the antinociceptive action demonstrated in the present study supports, at least partly, the ethnomedical uses of this plant.
Assuntos
Analgésicos/farmacologia , Melissa/química , Ácido Acético/toxicidade , Analgésicos/administração & dosagem , Analgésicos/isolamento & purificação , Animais , Arginina/farmacologia , Atropina/farmacologia , Cinamatos/farmacologia , Depsídeos/farmacologia , Relação Dose-Resposta a Droga , Feminino , Formaldeído/toxicidade , Ácido Glutâmico/toxicidade , Masculino , Mecamilamina/farmacologia , Camundongos , Atividade Motora/efeitos dos fármacos , Naloxona/farmacologia , Óxido Nítrico/fisiologia , Dor/induzido quimicamente , Dor/tratamento farmacológico , Dor/fisiopatologia , Limiar da Dor/efeitos dos fármacos , Limiar da Dor/fisiologia , Fitoterapia , Extratos Vegetais/administração & dosagem , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Folhas de Planta/química , Receptores Muscarínicos/efeitos dos fármacos , Receptores Muscarínicos/fisiologia , Receptores Nicotínicos/efeitos dos fármacos , Receptores Nicotínicos/fisiologia , Ácido RosmarínicoRESUMO
Gens. interações e retroações cibernéticamente organizadas, conjuntamente formam o tamanho da mandíbula. Evidências indicam que, biológicamente, cefalométricamente e terapeuticamente, a face das crianças corresponde a 6 categorias auxológicas de crescimento, 11 tipos rotacionais e 33 grupos rotacionais. Quanto maior a categoria auxológica, um aparelho ortodôntico é mais efetivo, a nível tecidual. O tratamento funcional de uma má-oclusão de Classe II é insuperávelmente melhor corrigido quando executado durante a fase ascendente da curva de crescimento pubertal. O início da aceleração de crescimento, em um dado menino, pode ser constatado pela medida da estatura corporal após os 7 ou 8 anos de idade, em intervalos de 3 meses