EFEITO DA SINVASTATINA NO TESTE DO COMPORTAMENTO ROTATÓRIO APÓS DESAFIO COM APOMORFINA EM UM MODELO ANIMAL DA DOENÇA DE PARKINSON

Edmar Miyoshi, Marissa Giovanna Schamne, Marcela Vaz Kuhn Minardi, Marcelo Machado Ferro

Resumo


A doença de Parkinson (DP) é a segunda doença neurodegenerativa mais comum na atualidade, e ainda não há nenhuma terapia eficaz para controlar a sua progressão, os tratamentos atuais apenas aliviam os sintomas. O objetivo desse trabalho foi avaliar o efeito da sinvastatina no comportamento rotatório de ratos com lesão unilateral pela 6-hidroxidopamina (6-OHDA). Ratos Wistar machos adultos receberam infusão unilateral de 6-OHDA no feixe prosencefálico medial (FPM) através de cirurgia estereotáxica. Em seguida, diferentes grupos de animais receberam diferentes doses de sinvastatina (1, 5 ou 25 mg/Kg) ou veículo, por via oral, diariamente por 28 dias. No 28° dia após a cirurgia, todos os animais foram submetidos ao teste do comportamento rotatório, induzido pela administração subcutânea (s.c.) de apomorfina (1 mg/Kg), no qual foram avaliados o número de rotações ipsi e contralaterais ao lado lesionado. Os animais do grupo 6-OHDA+veículo apresentaram um número maior de rotações contralaterais que os animais do grupo SHAM+veículo. Os animais dos grupos 6-OHDA+sinvastatina 1 mg/Kg e 6-OHDA+sinvastatina 5 mg/Kg apresentaram um menor número de rotações contralaterais, quando comparados com os animais do grupo 6-OHDA+veículo. Estes resultados sugerem que a sinvastatina pode diminuir ou impedir a morte de neurônios dopaminérgicos, portanto, possuir um efeito benéfico na doença de Parkinson. Este efeito pode estar ligado à conhecida ação anti-inflamatória da sinvastatina.

ABSTRACT

Parkinson's disease (PD) is currently the second most common neurodegenerative disease, and yet there is no effective therapy to control its progression, as current treatments only relieve symptoms. The aim of this study was to evaluate the simvastatin’s pharmacological effect on the rotational behavior in rats unilaterally lesioned by 6-hydroxydopamine (6-OHDA). Male adult Wistar rats received unilateral administration of 6-OHDA into de medial forebrain bundle, performed by stereotaxic surgery. Then, different groups received different doses of simvastatin (1, 5 and 25 mg/Kg) or vehicle, orally administrated on a daily basis for 28 days. On the 28th day after surgery, all animals were submitted to the turning behavior test, induced by subcutaneous administration of apomorphine (1 mg/Kg), in which the number of ipsilateral and contralateral rotations to the lesioned side rotations were analyzed. The 6-OHDA+vehicle animals showed an increased number of contralateral rotations when compared with SHAM+vehicle animals. The 6-OHDA+simvastatin 1 mg/Kg and 6-OHDA+simvastatin 5 mg/Kg animals showed a lower number of contralateral rotations compared to 6-OHDA+vehicle animals. These results suggest that simvastatin can reduce or prevent the death of dopaminergic neurons, and thus, have a beneficial effect on Parkinson’s disease. This effect may be related to the well-known simvastatin anti-inflammatory action.


Palavras-chave


doença de Parkinson; sinvastatina; neuroinflamação.

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