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IUBMB Life ; 72(8): 1765-1779, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32449271

RESUMO

Parkinson's disease (PD) induced by environmental toxins involves a multifactorial cascade of harmful factors, thus motivating the search for therapeutic agents able to act on the greatest number of molecular targets. This study evaluated the efficacy of 50 mg/kg purified anacardic acids (AAs), isolated from cashew nut shell liquid, on multiple steps of oxidative stress and inflammation induced by rotenone in the substantia nigra (SN) and striatum. Adult mice were divided into four groups: Control, rotenone, AAs + rotenone, and AAs alone. Lipoperoxidation, nitric oxide (NO) levels, and reduced glutathione (GSH)/oxidized gluthatione (GSSG) ratio were evaluated. NF-kB-p65, pro-IL-1ß, cleaved IL-1ß, metalloproteinase-9, Tissue Inhibitory Factor-1 (TIMP-1), tyrosine hydroxylase (TH), and glial fibrillary acidic protein (GFAP) levels were assessed by Western blot. In silico studies were also made using the SwissADME web tool. Rotenone increased lipoperoxidation and NO production and reduced TH levels and GSH/GSSG ratio in both SN and striatum. It also enhanced NF-kB-p65, pro, and cleaved IL-1ß, MMP-9, GFAP levels compared to control and AAs groups. The AAs alone reduced pro-IL-1ß in the striatum while they augmented TIMP1 and reduced MMP-9 amounts in both regions. AAs reversed rotenone-induced effects on lipoperoxidation, NO production, and GSH/GSSG ratio, as well as increased TH and attenuated pro-IL-1ß and MMP-9 levels in both regions, NF-kB-p65 in the SN and GFAP in the striatum. Altogether, the in vivo and in silico analysis reinforced multiple and defined molecular targets of AAs, identifying that they are promising neuroprotective drug candidates for PD, acting against oxidative and inflammatory conditions induced by rotenone.


Assuntos
Ácidos Anacárdicos/farmacologia , Fármacos Neuroprotetores/farmacologia , Doença de Parkinson Secundária/tratamento farmacológico , Doença de Parkinson/tratamento farmacológico , Praguicidas/toxicidade , Ácidos Anacárdicos/química , Ácidos Anacárdicos/isolamento & purificação , Animais , Simulação por Computador , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Corpo Estriado/patologia , Proteína Glial Fibrilar Ácida/genética , Glutationa/metabolismo , Dissulfeto de Glutationa/metabolismo , Humanos , Interleucina-1beta/genética , Peroxidação de Lipídeos/efeitos dos fármacos , Metaloproteinase 9 da Matriz/genética , Camundongos , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Doença de Parkinson/etiologia , Doença de Parkinson/genética , Doença de Parkinson/patologia , Doença de Parkinson Secundária/induzido quimicamente , Doença de Parkinson Secundária/genética , Doença de Parkinson Secundária/patologia , Inibidor Tecidual de Metaloproteinase-1/genética , Fator de Transcrição RelA/genética , Tirosina 3-Mono-Oxigenase/genética
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