Avaliação da atividade imunomoduladora da lectina de folhas Schinus terebinthifolius Raddi e do efeito sobre a formação de vasos do saco vitelínico e morfologia de embriões de Coturnix japonica

Abstract

Lectins, proteins that recognize carbohydrates, have been reported as potential immunomodulatory and antiangiogenic agents. Cancer, an important public health problem, is an example of a disease whose progress is associated with the processes of inflammation and angiogenesis. The high toxicity of currently available chemotherapeutic agents has stimulated the search for new compounds that are less toxic and more effective in treating tumors. Leaves of Schinus terebinthifolia Raddi (Anacardiaceae), the Brazilian peppertree, contains an antimicrobial lectin (SteLL). The present Thesis evaluated the effects of SteLL on the viability of mouse splenocytes and their ability to alter the production of cytokines and nitric oxide by these cells. The effect of the lectin on the angiogenesis process using as a model the Coturnix japonica embryos was also investigated. SteLL was not toxic to the splenocytes up to the concentration of 50 μg/mL, since no induction of apoptosis or necrosis was observed regarding the control. No significant changes were detected in the levels of cytosolic and mitochondrial oxygen reactive species and in the level of cytosolic calcium in the presence of SteLL (12.5 μg/mL); data that corroborate with the absence of cytotoxicity. On the other hand, a slight reduction in mitochondrial membrane potential (ΔΨm) was recorded. Treatment of splenocytes with SteLL (12.5 μg/mL) resulted in increased release of IL-17A, TNF-α, IFN-γ, IL-4 and IL-2 cytokines, indicating a predominantly proinflammatory response (Th1 and Th17). A small reduction in the nitric oxide production was also detected. Analysis by the Box Counting and Information Dimension methods revealed that SteLL (1.35 mg/mL) is an anti-angiogenic agent, since it inhibits the formation of new blood vessels from other pre-existing ones. The treatment with the lectin also reduced the percentage of cephalic length of C. japonica embryos, as well as their total area and perimeter, indicating morphological changes that corroborate the antiangiogenic effect. In conclusion, SteLL presented immunomodulatory action and interfered in the neovascularization of C. japonica embryos. These results stimulate future investigations of this lectin as a therapeutic agent to act in pathological conditions that involve the processes of inflammation and angiogenesis, such as cancer.