RESUMO
BACKGROUND: Chitosan, the N-deacetylated derivative of chitin, is a cationic polyelectrolyte due to the presence of amino groups, one of the few occurring in nature. The use of chitosan in protein and drug delivery systems is being actively researched and reported in the literature. RESULTS: In this study, we used chitosan-coated levodopa liposomes to investigate the behavioral character and the expression of phosphorylated extracellular signal-regulated kinase (ERK1/2), dopamine- and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32) and FosB/ΔFosB in striatum of rat model of levodopa-induced dyskinesia (LID). We found that scores of abnormal involuntary movement (AIM) decreased significantly in liposome group (P < 0.05), compared with levodopa group. Levels of phospho-ERK1/2, phospho-Thr34 DARPP-32 and FosB/ΔFosB in striatum decreased significantly in liposome group lesion side compared with levodopa group (P < 0.05). However, both of two groups above have significantly differences compared with the control group (P < 0.05). CONCLUSION: Chitosan-coated levodopa liposomes may be useful in reducing dyskinesias inducing for Parkinson disease. The mechanism might be involved the pathway of signaling molecular phospho-ERK1/2, phospho-Thr34 DARPP-32 and ΔFosB in striatum.
Assuntos
Quitosana/farmacologia , Dopaminérgicos/farmacologia , Fosfoproteína 32 Regulada por cAMP e Dopamina/metabolismo , Discinesia Induzida por Medicamentos/metabolismo , Discinesia Induzida por Medicamentos/prevenção & controle , Levodopa/farmacologia , Proteínas Proto-Oncogênicas c-fos/metabolismo , Animais , Materiais Biocompatíveis/farmacologia , Western Blotting , Corpo Estriado/efeitos dos fármacos , Fosfoproteína 32 Regulada por cAMP e Dopamina/análise , Fosfoproteína 32 Regulada por cAMP e Dopamina/efeitos dos fármacos , Discinesia Induzida por Medicamentos/etiologia , MAP Quinases Reguladas por Sinal Extracelular/análise , MAP Quinases Reguladas por Sinal Extracelular/efeitos dos fármacos , Imuno-Histoquímica , Lipossomos , Sistema de Sinalização das MAP Quinases , Masculino , Nanopartículas , Doença de Parkinson/tratamento farmacológico , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-fos/análise , Proteínas Proto-Oncogênicas c-fos/efeitos dos fármacos , Distribuição Aleatória , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Resultado do TratamentoRESUMO
BACKGROUND: Chitosan, the N-deacetylated derivative of chitin, is a cationic polyelectrolyte due to the presence of amino groups, one of the few occurring in nature. The use of chitosan in protein and drug delivery systems is being actively researched and reported in the literature RESULTS: In this study, we used chitosan-coated levodopa liposomes to investigate the behavioral character and the expression of phosphorylated extracellular signal-regulated kinase (ERK1/2), dopamine- and cAMP-regulated phos-phoprotein of 32 kDa (DARPP-32) and FosB/AFosB in striatum of rat model of levodopa-induced dyskinesia (LID). We found that scores of abnormal involuntary movement (AIM) decreased significantly in liposome group (P < 0.05), compared with levodopa group. Levels of phospho-ERK1/2, phospho-Thr34 DARPP-32 and FosB/AFosB in striatum decreased significantly in liposome group lesion side compared with levodopa group (P < 0.05). However, both of two groups above have significantly differences compared with the control group (P < 0.05). CONCLUSION: Chitosan-coated levodopa liposomes may be useful in reducing dyskinesias inducing for Parkinson disease. The mechanism might be involved the pathway of signaling molecular phospho-ERK1/2, phospho-Thr34 DARPP-32 and AFosB in striatum