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1.
Metab Brain Dis ; 35(1): 193-200, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31705440

RESUMO

Tyrosinemia type II is a genetic disorder characterized by elevated blood levels of the amino acid tyrosine caused by the deficiency of tyrosine aminotransferase enzyme, resulting in neurologic and developmental difficulties in the patients. Although neurological sequelae are common in Tyrosinemia type II patients, the mechanisms involved are still poorly understood. The oxidative stress appears to be, at least in part, responsible for neurological complication in this inborn error metabolism. We observed that an acute injection of tyrosine in rats caused a massive oxidative stress in different brain structures. The glutathione system and superoxide dismutase enzyme are relevant antioxidant strategies of the cells and tissues, including in the brain. Other important point is the strong relation between oxidative damage and inflammatory events. Herein, we investigated the effects of chronic administration of tyrosine in the hippocampus of young rats, with emphasis in the activity of GSH related enzymes and superoxide dismutase enzyme, and the astrocytosis. We observed that rats exposed to high levels of tyrosine presented an increased content of tyrosine, which was associated with an increment in the activity of glutathione peroxidase and glutathione reductase as well as with a diminished activity of superoxide dismutase. This antioxidant imbalance was accompanied by enhanced glial fibrillary acidic protein immunoreactivity, a marker of astrocytes, in the brain area studied. In conclusion, hippocampus astrogliosis is also a characteristic of brain alteration in Tyrosinemia. In addition, the chronic exposition to high levels of tyrosine is associated with an alteration in the activity of fundamental antioxidant enzymes.


Assuntos
Antioxidantes/metabolismo , Astrócitos/metabolismo , Gliose/metabolismo , Hipocampo/metabolismo , Tirosina/metabolismo , Tirosina/toxicidade , Animais , Animais Recém-Nascidos , Astrócitos/efeitos dos fármacos , Astrócitos/patologia , Esquema de Medicação , Gliose/induzido quimicamente , Gliose/patologia , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Masculino , Ratos , Ratos Wistar , Tirosina/administração & dosagem
2.
Behav Brain Res ; 312: 64-76, 2016 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-27306571

RESUMO

Dyskinesia consists in a series of trunk, limbs and orofacial involuntary movements that can be observed following long-term pharmacological treatment in some psychotic and neurological disorders such as schizophrenia and Parkinson's disease, respectively. Agmatine is an endogenous arginine metabolite that emerges as neuromodulator and a promising agent to manage diverse central nervous system disorders by modulating nitric oxide (NO) pathway, glutamate NMDA receptors and oxidative stress. Herein, we investigated the effects of a single intraperitoneal (i.p.) administration of different agmatine doses (10, 30 or 100mg/kg) against the orofacial dyskinesia induced by reserpine (1mg/kg,s.c.) in mice by measuring the vacuous chewing movements and tongue protusion frequencies, and the duration of facial twitching. The results showed an orofacial antidyskinetic effect of agmatine (30mg/kg, i.p.) or the combined administration of sub-effective doses of agmatine (10mg/kg, i.p.) with the NMDA receptor antagonists amantadine (1mg/kg, i.p.) and MK801 (0.01mg/kg, i.p.) or the neuronal nitric oxide synthase (NOS) inhibitor 7-nitroindazole (7-NI; 0.1mg/kg, i.p.). Reserpine-treated mice displayed locomotor activity deficits in the open field and agmatine had no effect on this response. Reserpine increased nitrite and nitrate levels in cerebral cortex, but agmatine did not reverse it. Remarkably, agmatine reversed the decrease of dopamine and non-protein thiols (NPSH) levels caused by reserpine in the striatum. However, no changes were observed in striatal immunocontent of proteins related to the dopaminergic system including tyrosine hydroxylase, dopamine transporter, vesicular monoamine transporter type 2, pDARPP-32[Thr75], dopamine D1 and D2 receptors. These results indicate that the blockade of NO pathway, NMDAR and oxidative stress are possible mechanisms associated with the protective effects of agmatine against the orofacial dyskinesia induced by reserpine in mice.


Assuntos
Agmatina/administração & dosagem , Discinesias/metabolismo , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Receptores de N-Metil-D-Aspartato/metabolismo , Reserpina/toxicidade , Animais , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Modelos Animais de Doenças , Maleato de Dizocilpina/farmacologia , Dopamina/metabolismo , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Fosfoproteína 32 Regulada por cAMP e Dopamina/metabolismo , Discinesia Induzida por Medicamentos/metabolismo , Discinesias/prevenção & controle , Antagonistas de Aminoácidos Excitatórios/farmacologia , Locomoção/efeitos dos fármacos , Masculino , Camundongos , Óxido Nítrico Sintase/metabolismo , Receptores Dopaminérgicos/metabolismo , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Tirosina 3-Mono-Oxigenase/metabolismo
3.
Rev. bras. farmacogn ; 25(1): 1-6, Jan-Feb/2015. tab, graf
Artigo em Inglês | LILACS | ID: lil-746060

RESUMO

Yerba-mate (Ilex paraguariensis A. St. Hil., Aquifoliaceae) is a South American native species that is widely used for its industrial potential in the preparation of drinks, teas and cosmetics. Its properties are directly related to the presence of its chemical constituents, such as saponins, methylxanthines and phenolic compounds. This study aimed to investigate the influence of leaf age on methylxanthine and total phenolic contents by High Performance Liquid Chromatography and Ultraviolet Spectroscopy, as well as on free radical scavenging capacity, of aqueous extracts of I. paraguariensis leaves. The results showed great variability in all the metabolites measured. Leaf ageing significantly increased the methylxanthine content and total phenolic content of the extracts. Free radical scavenging capacity was also significantly affected (p < 0.05) by leaf age. A positive correlation was observed, between the antioxidant activity and total phenolic content.

4.
J Med Food ; 17(3): 324-31, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24476224

RESUMO

The antibiofilm and antibacterial properties against Pseudomonas aeruginosa and Staphylococcus epidermidis and chemical characterization of six hydroethanolic blueberry extracts (blueberry rabbiteye-Vaccinium virgatum) from different cultivars and means of propagation were investigated. The total flavonoid, anthocyanin, and phenolic contents were determined by specific and well-established methods. Among the cultivars, Briteblue showed the lowest content of all metabolites analyzed, while Bluegem showed the highest concentrations of these compounds. All the micropropagated cultivars presented the highest amounts of chlorogenic acid. The blueberry fruit extracts showed strong activity against S. epidermidis biofilm (up to 84% inhibition) without inhibiting bacterial growth. Likewise, Bluegem micropropagated extract, which had the highest anthocyanin, flavonoids, and phenolic compound content, demonstrated the highest S. epidermidis biofilm inhibitory effect. Finally, a linear correlation between the total phenolic content and the percentage of biofilm inhibition was observed.


Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Mirtilos Azuis (Planta)/química , Extratos Vegetais/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus epidermidis/efeitos dos fármacos , Frutas/química , Pseudomonas aeruginosa/fisiologia , Staphylococcus epidermidis/fisiologia
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