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1.
Behav Pharmacol ; 29(4): 336-343, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29239973

RESUMO

Studies have shown that hydrogen sulfide (H2S) exerts a neuroprotective effect and may have a therapeutic value for treating neurodegenerative diseases including Parkinson's disease. However, little is known about the mechanisms underlying the neuroprotective activity of H2S in vivo. Here, we evaluated the effect of glibenclamide, an ATP-sensitive potassium channel blocker, on the neuroprotective activity of H2S in the 6-hydroxydopamine (6-OHDA) animal model of Parkinson's disease. 6-OHDA was administered by stereotaxic surgery into the medial forebrain bundle. Sodium hydrosulfate (NaHS, 3 and 5.6 mg/kg), as a donor of H2S, alone or in combination with glibenclamide (5 mg/kg), was daily injected for 7 days starting 1-2 h before the stereotaxic surgery. After an apomorphine-induced rotational test, the number of tyrosine hydroxylase-positive neurons in the substantia nigra pars compacta was determined by immunofluorescence. The striatal dopamine level and oxidative stress markers were also measured in brain homogenates. Pretreatment with NaHS significantly attenuated 6-OHDA-induced motor asymmetry in the rotational test. Histological and biochemical evaluations demonstrated that NaHS, especially at high dose, increased the survival of tyrosine hydroxylase-positive neurons in the substantia nigra pars compacta and reduced the decreasing effect of 6-OHDA on striatal dopamine levels. However, co-administration of glibenclamide reversed the antiparkinsonian and neuroprotective effects of NaHS. However, glibenclamide did not change the reducing effect of NaHS on 6-OHDA-induced overproduction of malondialdehyde. Our data show that ATP-sensitive potassium channels are involved in the antiparkinsonian and neuroprotective effects of H2S in the 6-OHDA animal model of Parkinson's disease.


Assuntos
Sulfeto de Hidrogênio/farmacologia , Canais KATP/fisiologia , Doença de Parkinson/tratamento farmacológico , Trifosfato de Adenosina/fisiologia , Animais , Apomorfina/farmacologia , Corpo Estriado/metabolismo , Modelos Animais de Doenças , Dopamina , Agonistas de Dopamina/farmacologia , Sulfeto de Hidrogênio/uso terapêutico , Canais KATP/efeitos dos fármacos , Masculino , Doenças Neurodegenerativas/patologia , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Oxidopamina/farmacologia , Doença de Parkinson/metabolismo , Canais de Potássio/efeitos dos fármacos , Ratos , Ratos Wistar , Substância Negra/efeitos dos fármacos
2.
Int J Androl ; 32(4): 417-22, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19515171

RESUMO

Abnormal levels of androgens cause many diseases like benign prostatic hyperplasia and hormone dependent cancers. Although the reduction in serum testosterone (T) by Glycyrrhiza glabra has been reported, its effects on seminal vesicle (SV) and prostate tissues have never been reported. This study was carried out to investigate different aspects of antiandrogenic properties of this plant. Immature male rats were divided into five groups (n = 7): castrated rats without any treatment received only vehicle; castrated rats plus T replacement; three castrated groups with T replacement plus various doses of G. glabra extract (75, 150 and 300 mg/kg). All of the injections were carried out once daily in subcutaneous manner for 7 days. On the eighth day, blood samples were collected for total T measurement. Ventral prostate (VP), SV and levator ani muscle were dissected and weighed. Slides prepared from prostate were assessed histologically. The variation in the relative and absolute volume of the prostate tissue compartments was determined. Those receiving the doses of 150 and 300 mg/kg showed a significant reduction (p < 0.05) in prostate weight, total T and VP epithelium/stroma ratio (V/V). These results in SV and levator ani were shown in response to 300 mg/kg of extract. Increasing in T metabolism, down-regulation of androgen receptors or activation of oestrogen receptors could be involved mechanisms. This study showed that alcoholic extract of G. glabra has antiandrogenic properties.


Assuntos
Antagonistas de Androgênios/farmacologia , Glycyrrhiza , Terapia de Reposição Hormonal , Extratos Vegetais/farmacologia , Próstata/efeitos dos fármacos , Glândulas Seminais/efeitos dos fármacos , Testosterona/administração & dosagem , Antagonistas de Androgênios/administração & dosagem , Animais , Relação Dose-Resposta a Droga , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Injeções Subcutâneas , Masculino , Orquiectomia , Tamanho do Órgão , Extratos Vegetais/administração & dosagem , Próstata/patologia , Ratos , Ratos Wistar , Glândulas Seminais/patologia , Células Estromais/efeitos dos fármacos , Células Estromais/patologia , Testosterona/sangue
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