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1.
Toxins (Basel) ; 8(3)2016 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-26978403

RESUMO

The in vivo neuroprotective effect of PhTx3-4, a spider toxin N-P/Q calcium channel blocker, was studied in a rat model of NMDA-induced injury of the retina. NMDA (N-Methyl-D-Aspartate)-induced retinal injury in rats reduced the b-wave amplitude by 62% ± 3.6%, indicating the severity of the insult. PhTx3-4 treatment increased the amplitude of the b-wave, which was almost equivalent to the control retinas that were not submitted to injury. The PhTx3-4 functional protection of the retinas recorded on the ERG also was observed in the neuroprotection of retinal cells. NMDA-induced injury reduced live cells in the retina layers and the highest reduction, 84%, was in the ganglion cell layer. Notably, PhTx3-4 treatment caused a remarkable reduction of dead cells in the retina layers, and the highest neuroprotective effect was in the ganglion cells layer. NMDA-induced cytotoxicity of the retina increased the release of glutamate, reactive oxygen species (ROS) production and oxidative stress. PhTx3-4 treatment reduced glutamate release, ROS production and oxidative stress measured by malondialdehyde. Thus, we presented for the first time evidence of in vivo neuroprotection from NMDA-induced retinal injury by PhTx3-4 (-ctenitoxin-Pn3a), a spider toxin that blocks N-P/Q calcium channels.


Assuntos
Bloqueadores dos Canais de Cálcio/uso terapêutico , Neuropeptídeos/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Doenças Retinianas/tratamento farmacológico , Venenos de Aranha/uso terapêutico , Animais , Bloqueadores dos Canais de Cálcio/farmacologia , Eletrorretinografia , Ácido Glutâmico/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , N-Metilaspartato , Neuropeptídeos/farmacologia , Fármacos Neuroprotetores/farmacologia , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Doenças Retinianas/induzido quimicamente , Doenças Retinianas/metabolismo , Doenças Retinianas/fisiopatologia , Venenos de Aranha/farmacologia , Corpo Vítreo/metabolismo
2.
Toxicon ; 108: 53-61, 2015 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-26435340

RESUMO

Venom-derived peptides constitute a unique source of drug prototypes for the pain management. Many of them can modulate voltage-gated calcium channels that are central in the processing of pain sensation. PhTx3-4 is a peptide isolated from Phoneutria nigriventer venom, which blocks high voltage-activated calcium channels with low specificity, thereby leading to neuroprotection in models of ischemia in vitro. The aim of the present work was evaluating the potential of intrathecal PhTx3-4 in the reversal of different nociceptive states in mice, furthermore assessing the potential of PhTx3-4 in triggering motor side effects. We found that bellow 100 pmol/site, PhTx3-4 did not cause major motor side effects. By comparison, ω-conotoxin MVIIA and ω-conotoxin MVIIC triggered motor side effects at the doses of 10 and 100 pmol/site, respectively. Also, PhTx3-4 (30 pmol/site) caused no significant alterations in the forced locomotor activity test (rotarod) and in the exploratory activity test (versamax). In a model of inflammatory persistent pain (formalin test), PhTx3-4 reversed nociceptive behavior both pre or post-administered, although this effect was observed only at the inflammatory phase of the test and not at the neurogenic phase. Comparatively, ω-conotoxin MVIIC was effective only when post-administered in the formalin test. Nonetheless, PhTx3-4 treatment was devoid of action in acute nociceptive thermal model (hotplate test), whereas morphine showed efficacy in this test. Efficacy of PhTx3-4 in the formalin test was associated with inhibition of formalin-induced glutamate release in the cerebrospinal fluid. PhTx3-4, but not ω-conotoxin MVIIC, reversed NMDA-induced nociceptive behavior indicating a putative role of PhTx3-4 at ionotropic glutamate receptors. Finally, we observed efficacy of PhTx3-4 in ameliorating mechanical hypersensitivity induced by paw incision, a post-operative and more clinically relevant pain model. Taken together, our data show that PhTx3-4 possesses antinociceptive effect in different models of pain in mice, suggesting that this toxin may serve as drug prototype for pain control.


Assuntos
Analgésicos/farmacologia , Neuropeptídeos/farmacologia , Neurotoxinas/farmacologia , Dor/tratamento farmacológico , Venenos de Aranha/farmacologia , Analgésicos/efeitos adversos , Analgésicos/uso terapêutico , Animais , Masculino , Camundongos , Neuropeptídeos/efeitos adversos , Neuropeptídeos/uso terapêutico , Neurotoxinas/efeitos adversos , Neurotoxinas/uso terapêutico , Dor/prevenção & controle , Venenos de Aranha/efeitos adversos , Venenos de Aranha/uso terapêutico , Aranhas/química
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