Estudo do efeito da rutina na motilidade gastrointestinal em modelo pré-clínico da Doença de Parkinson induzido por aminocromo

Abstract

Parkinson's disease (PD) is a public health problem that affects many individuals in the world, including Brazil. It is a neurodegenerative disease of slow progression that mainly affects the elderly population. Although scientific research has advanced in order to seek effective treatments for this pathology, there is no therapy capable of curing or inhibiting the progression of the disease. The scientific community has been prospecting neuroprotective compounds, which inhibit dysfunctions and death in cells involved in PD pathogenesis; among them, it is possible to cite the flavonoid rutin, which has had neuroprotective potential against glutamatergic excitotoxicity and cytotoxicity induced by 6-hydroxydopamine. However, the lack of information on the disease's etiology makes difficult advances in the discovery of new drugs to treat PD. An important change that precedes the classic motor symptoms of PD is the disorder in gastrointestinal motility, associated with changes in the enteric nervous system, which also has an unknown etiology. In vitro and in vivo study models have revealed that many cellular and molecular changes present in patients with the disease are related to aminochrome toxicity, a compound derived from dopamine and precursor of neuromelanine, present in remnant dopaminergic neurons. However, there is still no report that it is able to induce changes in the enteric function. The overall objective of this project was to evaluate the effect of rutin in Wistar rats with damage induced by aminochrome in terms of: 1- levels of dopaminergic neuron marker expression (tyrosine hydroxylase) in the ventral tegmental area (VTA) and substantia nigra pars compacta (SNpc) and 2- gastrointestinal traffic time. The animals were randomized in four groups: control group (CTR), aminochrome (AMI), rutin (RUT) and aminochrome + rutin (AMI+RUT). Rutin was administered by gavage, from the first to the twentieth first day after stereotaxis. The living weight of the animals was evaluated from the day of stereotaxic surgery until the time of perfusion. Intestinal transit time was evaluated by the carmine red test, aiming to analyze the functional changes induced by the treatments. As a result, rutin promoted a reduction in intestinal timely time compared to the control group. The aminochrome also reduced the expression of tyrosine hydroxylase (TH+) on the ipsilateral side of the SNpc, which was prevented by rutin treatment. However, no change in TH+ expression in VTA of animals treated with aminochrome and/or rutin was observed. Rutin promoted a reduction in the weight of treated animals, with a modulatory role in weight regulation. Thus, studies are necessary to evaluate the incited biochemical mechanisms for such modulation, which is important for further research using preclinical DP models.