RESUMO
Recent reports have shown that commercial orange juice is rich in biogenic amines. Consumption of foods containing large amounts of biogenic amines increase hypertensive crisis and high levels of histamine and tyramine, which have been implicated as causative agents in a number of food poisoning episodes. In addition, accumulation of tryptamine in plasma may be associated with mood disorders. The aim of this study was to determine whether chronic administration of orange juice extract and tryptamine affects the behavior and c-fos expression in the rat. For this purpose, Wistar male rats were injected with saline solution, tryptamine or orange juice extract. Sucrose preference test and elevated plus maze were evaluated to determine hedonic and anxiety behavior, respectively. Rats treated with orange juice extract showed increased anxiety behavior and sucrose consumption, similar to those treated with tryptamine. In addition, dorsal raphe nucleus, accumbens nucleus, and hippocampus showed an increase of c-fos positive cells in rats treated with orange juice extract. In conclusion, the chronic and lengthy consumption of orange juice or their derivatives in the diet could be a factor responsible to induce mood disorders and may promote excess caloric consumption.
Assuntos
Comportamento Animal/fisiologia , Sucos de Frutas e Vegetais , Proteínas Proto-Oncogênicas c-fos/metabolismo , Triptaminas/metabolismo , Animais , Citrus sinensis/metabolismo , Masculino , Núcleo Accumbens/efeitos dos fármacos , Ratos Wistar , SacaroseRESUMO
In order to understand the interaction between naratriptan and a fully hydrated bilayer of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidyl-choline (POPC), we carried out molecular dynamics simulations. The simulations were performed considering neutral and protonated ionization states, starting from different initial conditions. At physiological pH, the protonated state of naratriptan is predominant. It is expected that neutral compounds could have larger membrane partition than charged compounds. However, for the specific case of triptans, it is difficult to study neutral species in membranes experimentally, making computer simulations an interesting tool. When the naratriptan molecules were originally placed in water, they partitioned between the bilayer/water interface and water phase, as has been described for similar compounds. From this condition, the drugs displayed low access to the hydrophobic environment, with no significant effects on bilayer organization. The molecules anchored in the interface, due mainly to the barrier function of the polar and oriented lipid heads. On the other hand, when placed inside the bilayer, both neutral and protonated naratriptan showed self-aggregation in the lipid tail environment. In particular, the protonated species exhibited a pore-like structure, dragging water through this environment. Graphical Abstract Different behaviour of Naratriptan and Sumatriptan, when the drugs were originally placed in the lipid core.
Assuntos
Bicamadas Lipídicas/química , Simulação de Dinâmica Molecular , Piperidinas/metabolismo , Triptaminas/metabolismoRESUMO
To evaluate the protector effect of ascorbic acid (AA) against anxiogenic-like effect induced by methylmercury (MeHg) exposure, adult zebrafish were treated with AA (2 mg g(-1), intraperitoneal [i.p.]) before MeHg administration (1.0 µg g(-1), i.p.). Groups were tested for the light/dark preference as a behavioral model of anxiety, and the content of serotonin and its oxidized metabolite tryptamine-4,5-dione (T-4,5-D) in the brain was determined by high-performance liquid chromatography. MeHg has produced a marked anxiogenic profile in both tests, and this effect was accompanied by a decrease in the extracellular levels of serotonin, and an increase in the extracellular levels of T-4,5-D. Added to this, a marked increase in the formation of a marker of oxidative stress accompanied these parameters. Interestingly, the anxiogenic-like effect and biochemical alterations induced by MeHg were blocked by pretreatment with AA. These results for the first time demonstrated the potential protector action of AA in neurobehavioral and neurochemical alterations induced by methylmecury exposure demonstrating that zebrafish model could be used as an important tool for testing substances with neuroprotector actions.
Assuntos
Antioxidantes/farmacologia , Ansiedade/induzido quimicamente , Ácido Ascórbico/farmacologia , Encéfalo/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Compostos de Metilmercúrio/toxicidade , Peixe-Zebra/metabolismo , Animais , Encéfalo/metabolismo , Cromatografia Líquida de Alta Pressão , Indolquinonas/metabolismo , Serotonina/metabolismo , Triptaminas/metabolismoRESUMO
During inflammatory events, neutrophils and platelets interact to release a variety of mediators. Neutrophils generate superoxide and hydrogen peroxide, and also discharge the haem enzyme myeloperoxidase. Among numerous other mediators, platelets liberate serotonin (5-hydroxytryptamine), which is a classical neurotransmitter and vasoactive amine that has significant effects on inflammation and immunity. In the present study, we show that serotonin is a favoured substrate for myeloperoxidase because other physiological substrates for this enzyme, including chloride, did not affect its rate of oxidation. At low micromolar concentrations, serotonin enhanced hypochlorous acid production by both purified myeloperoxidase and neutrophils. At higher concentrations, it almost completely blocked the formation of hypochlorous acid. Serotonin was oxidized to a dimer by myeloperoxidase and hydrogen peroxide. It was also converted into tryptamine-4,5-dione, especially in the presence of superoxide. This toxic quinone was produced by stimulated neutrophils in a reaction that required myeloperoxidase. In plasma, stimulated human neutrophils oxidized serotonin to its dimer using the NADPH oxidase and myeloperoxidase. We propose that myeloperoxidase will oxidize serotonin at sites of inflammation. In doing so, it will impair its physiological functions and generate a toxic metabolite that will exacerbate inflammatory tissue damage. Consequently, oxidation of serotonin by myeloperoxidase may profoundly influence inflammatory processes.
Assuntos
Indolquinonas/metabolismo , Peroxidase/metabolismo , Serotonina/metabolismo , Superóxidos/metabolismo , Triptaminas/metabolismo , Catálise/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Citotoxinas/metabolismo , Dimerização , Inibidores Enzimáticos/farmacologia , Sequestradores de Radicais Livres/farmacologia , Humanos , Peróxido de Hidrogênio/metabolismo , Ácido Hipocloroso/metabolismo , Espectrometria de Massas , Neutrófilos/citologia , Neutrófilos/metabolismo , Oxirredução/efeitos dos fármacos , Peroxidase/antagonistas & inibidores , Serotonina/química , Especificidade por SubstratoRESUMO
Biotransformation of tryptophan to tryptamine and 3-methyl-indole by Psilocybe coprophila was performed. On the other hand, Aspergillus niger was able to transform tryptophan to 5-hydroxy-tryptophan. P. coprophila biotransformed 5-hydroxy-tryptophan to 5-hydroxytryptamine. These results prove once more that fungi are good tools to establish hydroxyindole derivatives.
Assuntos
Aspergillus niger/metabolismo , Basidiomycota/metabolismo , Indóis/metabolismo , Triptofano/metabolismo , Biotransformação , Especificidade da Espécie , Triptaminas/metabolismoRESUMO
Chemical reactions performed by fungi have been used as a modern tool in chemistry. In this work, we show the tryptophan biotransformation with Psilocybe coprophila on liquid culture medium. The results prove once more the versatility of fungi in performing a wide range of industrially attractive chemical reactions.
Assuntos
Basidiomycota/citologia , Triptofano/metabolismo , Alcaloides/isolamento & purificação , Biotransformação , Células Cultivadas , Meios de Cultura , Espectroscopia de Ressonância Magnética , Triptaminas/metabolismoRESUMO
The prevalence of migraine is high, affecting a significant proportion of the adult population during their most productive years of life and promoting impairment of their normal daily activities. Although guidelines for the acute treatment of migraine are available, outcome parameters are sometimes still below the expectations of both patients and physicians. Triptans represented an advance in clinical practice and have become the most well-studied class of medication for migraine. These agents present class I evidence for efficacy. However, they differ with regard to several of their clinical parameters, including onset of relief and consistency of response. Rizatriptan is a selective agonist of the 5-hydroxytryptophan(1B/1D )receptors, with proven superiority over placebo, ergotamine and selected oral triptans, demonstrating a good profile of safety and tolerability.
Assuntos
Transtornos de Enxaqueca/tratamento farmacológico , Agonistas do Receptor de Serotonina/uso terapêutico , Triazóis/uso terapêutico , Triptaminas/uso terapêutico , Relação Dose-Resposta a Droga , Tolerância a Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Prova Pericial , Humanos , Metanálise como Assunto , Agonistas do Receptor de Serotonina/química , Agonistas do Receptor de Serotonina/metabolismo , Agonistas do Receptor de Serotonina/farmacologia , Triazóis/química , Triazóis/metabolismo , Triazóis/farmacologia , Triptaminas/química , Triptaminas/metabolismo , Triptaminas/farmacologiaRESUMO
Intraerythrocytic malaria parasites develop in a highly synchronous manner. We have previously shown that the host hormone melatonin regulates the circadian rhythm of the rodent malaria parasite, Plasmodium chabaudi, through a Ca2+-based mechanism. Here we show that melatonin and other molecules derived from tryptophan, i.e. N-acetylserotonin, serotonin and tryptamine, also modulate the cell cycle of human malaria parasite P. falciparum by inducing an increase in cytosolic free Ca2+. This occurs independently of the extracellular Ca2+ concentration, indicating that these molecules induce Ca2+ mobilization from intracellular stores in the trophozoite. This in turn leads to an increase in the proportion of schizonts. The effects of the indolamines in increasing cytosolic free Ca2+ and modulating the parasite cell cycle are both abrogated by an antagonist of the melatonin receptor, luzindole, and by the phospholipase inhibitor, U73122.
Assuntos
Cálcio/metabolismo , Ciclo Celular/fisiologia , Plasmodium falciparum/citologia , Plasmodium falciparum/fisiologia , Triptofano/fisiologia , Animais , Células Cultivadas , Eritrócitos/metabolismo , Eritrócitos/parasitologia , Humanos , Plasmodium falciparum/crescimento & desenvolvimento , Serotonina/metabolismo , Serotonina/fisiologia , Triptaminas/metabolismo , Triptaminas/fisiologia , Triptofano/metabolismoRESUMO
Psychotria viridis and P. carthagenensis are often discussed in relation to the hallucinogenic beverage Ayahuasca, used for religious, medicinal and social purposes. The significance of including Psychotria species in this beverage has been understood on the basis of substantial amounts of tryptamine alkaloids detected on leaves of both P. viridis and P. carthagenensis. Nevertheless, there is a long lasting debate over the identification of which Psychotria species are actually traditionally employed. We here report that a P. carthagenensis leaf ethanol extract was found to be devoid of alkaloids. The extract significantly decreased mice body temperature (350 and 500 mg/kg). Toxicity assessment revealed that the extract induced sedation and slight ptoses (75% of animals treated with 1000 mg/kg). Lethality was not observed within 48 h. The data indicate that P. carthagenensis does have bioactive compound(s), possibly active at the central nervous system, but unlikely to be tryptamine alkaloids as in the case of P. viridis. Therefore, if P. carthagenensis is indeed used by ayahuasqueros, its chemical and pharmacological significance have yet to be elucidated.
Assuntos
Alucinógenos/farmacologia , Análise de Variância , Animais , Bebidas , Temperatura Corporal/efeitos dos fármacos , Sistema Nervoso Central/efeitos dos fármacos , Etanol/química , Alucinógenos/administração & dosagem , Alucinógenos/toxicidade , Hipnóticos e Sedativos/toxicidade , Masculino , Camundongos , Extratos Vegetais/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/toxicidade , Folhas de Planta/metabolismo , Intoxicação/mortalidade , Triptaminas/análise , Triptaminas/metabolismoRESUMO
An alkaloidal fraction was obtained from Mimosa tenuiflora (Willd.) Poir (tepescohuite) trunk bark. The product contained mainly an indolealkylamine and three minor alkaloids. This fraction inhibited the peristaltic reflex in the guinea-pig isolated ileum in vitro.