AVALIAÇÃO DO PTEROSTILBENO PARA TRATAMENTO NA FASE AGUDA DE ARTRITE REUMATOIDE

Abstract

Rheumatoid arthritis (RA) is one of the most prevalent chronic inflammatory diseases that primarily involves the joints and may include extra-articular manifestations such as nodules, pulmonary involvement, vasculitis, and systemic comorbidities. Regarding inflammatory symptoms, joint swelling is caused by inflammation of the synovial membrane due to activation of the immune system, characterized by infiltration of leukocytes. Pterostilbene (PTE) can be found in blueberries and grapes, from plants belonging to the Vitis and Vaccinium families. It has anti-hypertensive activities; anticancer; antihypercholesterolemic; antidiabetics; antioxidants and anti-inflammatory. The aim of this project was to verify if pterostilbene has superior activity, as well as the basic mechanism of action of resveratrol. The drug was suspended in carboxymethylcellulose (CMC) (1%) at different concentrations (4 mg/kg; 200 mg/kg; 400 mg/kg) to be administered orally. Forty-five rats of the Rattus Norvegicus breed, Wistar lineage were used, the animals were divided into 3 groups with a group with 5, another 10 and another with 30 rats, corresponding, respectively, to the Control Group (CG); SHAM Group (SHAM) and Pterostilbene Group (GP), the SHAM and GP groups were subdivided into: with joint damage, and with and without treatment with an oral solution of Pterostilbene; groups were subdivided into 0 (with euthanasia 12 hours after induction) and 3 days (with euthanasia 72 hours after). Histological analyzes were performed to evaluate the pathological aspects, observing the characteristics of the epithelial changes and inflammatory infiltrate, type, and a number of cells, in addition to neovascularization and fibroblasts. Analyzes of inflammatory cytokines by flow cytometry were also performed. An acute inflammatory process, diffusely with mild to moderate intensity, characterizes lesions. In the 12h histological sections, it was observed that the treated groups presented a mild amount of mononuclear inflammatory cells (MN) and a moderate amount of polymorphonuclear cells (PM). It was also observed proliferative phenomena of an increasing form of fibroblasts up to the group treated with 400 mg/kg. In the 72h sections, it was observed that the groups treated with 4 mg/kg and 400 mg/kg presented moderate levels of PM, and light concentration of MN. At 200 mg/kg, there was a moderate concentration for both cell forms. Regarding neovascularization, it was observed that in all groups there was a mild process of angiogenesis As for the analysis by flow cytometry, the analyzes were divided by the data from the Th1/Th2 kit and the inflammation kit. In the Th1/Th2 analyses, the levels of tumor necrosis factor (TNF) were slightly increased, as is characteristic of RA, and due to the MN that are involved in the process of stimulating the production of TNF in the Th1 pathway. In the levels of interferon-γ (IFN-γ), there was a slight increase corroborating the histology where MN that induce its production was found. Interleukin (IL) 2 levels increased in concentrations in the 12h and 72h groups, with the exception of GP1, in relation to the initial 0h assessment; it can be explained due to stimulated production by T cells and IL-12 levels. IL-4 was increased in all groups compared to the initial assessment and the treatment may have provided an increase in this IL in groups treated with the highest concentrations of PTE after 72 hours of injury. IL-5 values were decreased in all groups compared to control, and having an increase in groups GP50 and GP100 72h in relation to the initial values (0h); the lowest levels found may be due to inhibition by IFN. In the analysis with inflammation kit, it was observed that TNF levels were increased because cells such as macrophages and neutrophils would be involved in the production process. IFN-γ levels increased in all treated groups compared to control; they may be related to the stimulation made by IL-12 and MN. IL-6 was also increased in all treated groups compared to control and is linked to the promotion and maturation of inflammatory cells. IL-12p70 levels increased in concentrations both in the 12h and 72h groups in relation to the initial 0h assessment and to the control; the increased levels are expected in RA as it participates in the Th1 pathway activation cascade. IL-10 levels increased slightly in all treated groups compared to the control, its levels may be due to the probable inhibition of its production, which may occur by the action of IL-10 itself, IL-4, and IFN-γ. The levels of monocyte chemotactic protein (MCP)-1 increased in all treated groups compared to control; with a significant increase in the group treated with 400 mg/kg corroborating the histology that presented an intense amount of fibroblasts after 72h. It is concluded that Pterostilbene, by having a proven anti-inflammatory activity, promoted a balance in the inflammatory process seen by the concentration of the evaluated interleukins, their activities, and correlations with a tendency of efficient inflammatory control so that there is no exacerbation of symptoms and lesions; in addition to stimulating structural restoration through the high production of fibroblasts and angiogenesis.