Envolvimento do estresse oxidativo e dos sistemas colinérgico e purinérgico na esclerose múltipla: estudo clínico e de revisão

Abstract

Multiple sclerosis (MS) is one of the main chronic inflammatory diseases of the central nervous system (CNS) that cause functional disability in young adults. It is considered one complex autoimmune and neurodegenerative illness, since it has several processes involved in its arrival, including inflammation, demyelination, axonal damage and repair mechanisms. Studies have suggested that there is a close relationship between an increase of the pro-oxidants agents, the presence of pro-inflammatory events and modifications in the immune response. Thus, the aim of this study was to verify oxidative stress biomarkers such as levels of thiobarbituric acid reactive substances (TBARS), protein carbonyl content in serum, DNA damage in leukocytes, as well as the activity of superoxide dismutase (SOD), catalase (CAT) and delta-aminolevulinate dehydratase (δ-ALA-D) enzymes in whole blood. Additionally, we determined the levels of non-enzymatic antioxidants, such as vitamin C, vitamin E, non-protein thiol (NPSH) and vitamin D in serum. For this study, two groups were evaluated: EM group composed of patients diagnosed with the relapsing-remitting form of MS (RRMS) and Control Group (CG), composed of healthy volunteers. The results showed increase CAT activity simultaneously the reduction in the activity of SOD in whole blood from RRMS patients when compared with healthy subjects. Likewise, we observed an elevation in levels lipid peroxidation and carbonyl protein in serum as well as the increase DNA damage in leukocytes from RRMS patients when compared to GC. Another important finding was the elevation of δ-ALA-D activity in whole blood in RRMS patients compared to GC. Furthermore, the vitamin C, vitamin E, NPSH and vitamin D levels were significantly decreased in RRMS individuals when compared to GC. In addition, we sought to analyze the involvement of the cholinergic and purinergic systems in both patients and experimental models of MS because these systems seem to have a significant influence on the activation and maintenance of the immune system besides they participate in the control and resolution of the response inflammatory. In this scenario, an extensive review of the existing findings in the scientific literature and it showed through a review article the relevant implication of these systems in the pathogenesis of MS. Thus, the results obtained from these studies suggest that there is an alteration in the oxidative/antioxidant balance in patients with RRMS, we evidenced by the response found through oxidative stress biomarkers. In addition, the cholinergic and purinergic systems influence the mechanisms that signal, regulate and control inflammatory and immune responses in MS, therefore the association of these factors could cooperate to the onset and/or trigger the outbreaks in MS. Also, it is suggested the existence of a continuous pro-inflammatory response both central and peripheral. Taken together, these findings contribute to a better understanding of the etiopathogenic mechanisms involved in this disease besides may be useful to extend the therapeutic and monitoring of this neurodegenerative disorder in benefit of the quality of life of MS individuals.