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DETERMINATION OF THE EFFECTS OF TREATMENT OF RATS WITH LPS IN THE PRODUCTION OF REACTIVE OXYGEN SPECIES AND ANTIOXIDANT SYSTEMS IN PLATELETS: ROLE OF THESE SYSTEMS IN THE MODULATION OF PLATELET REACTIVITY
The severe sepsis is responsible for numerous cases admitted to hospitals, many of whom died, and is triggered primarily by gram-negative and gram-positive. The gram-negative bacteria trigger most of its effects through the lipopolysaccharide (LPS). The LPS can activate many types of cells leading to activation of nuclear factor kB (NF-kB) that increases the expression of specific genes that encode proteins related to inflammatory response such as cytokines, adhesion proteins and enzymes such as cyclooxygenase 2 (COX-2 ) and nitric oxide synthase (iNOS). During sepsis is also the generation of large amounts of reactive oxygen species (ROS) like superoxide anion (O2-) hydrogen peroxide (H2O2) and hydroxyl radical (. OH) and reactive nitrogen species (NRS) as the oxide oxide (NO) and peroxynitrite (ONOO-) coming from the reaction between NO and O2-. Evidence indicates the involvement of ROS and NRS in the pathogenesis of sepsis leading to multiple organ failure. Another event that occurs in the initial phase of endotoxemia is a significant decrease in the number of leukocytes and platelets in peripheral blood. In humans, there is a positive correlation between the number and activation state of platelets with the severity of sepsis. Some studies have been performed describing the effects of LPS on platelets, however, the results are still quite controversial. Platelet activation leads to activation of a number of signaling pathways including those involving the Src kinase and phosphatidylinositol 3-kinase (PI3K), which contribeum for firm adherence and platelet aggregate stabilization. Research shows that these enzymes can modulate the formation of ROS in different cells and are also responsible for mediating some effects of LPS. However, no work has been published so far on the effect of LPS on intracellular signaling via Src and PI3K in platelets. Therefore, we propose in this work, to investigate the sources of ROS and antioxidant systems in platelets of rats treated with LPS. In addition, we intend to study the modulatory role of Src and PI3K on the production of ROS in platelets of these animals.
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