, 2010) Among the glycation agents we call attention to methylgl

, 2010). Among the glycation agents we call attention to methylglyoxal, which is a dicarbonyl reactive that originates from the breakdown of glucose (Desai and Wu, 2007). The results of this study showed that co-treatment of human neutrophils with MGO/high glucose promoted important modifications in the neutrophil function in vitro. Treatment of neutrophils with MGO/high glucose

did not promote citotoxicity; however, it reduced the NVP-BKM120 molecular weight phagocytic capacity and the G6PDH, total/SOD and GR activities. Additionally, there was an increase in the activity of myeloperoxidase (MPO) with consequent increase in the hypochlorous acid production, CAT activity and in the release of IL-6 cytokine without changes in intracellular calcium mobilization. Contrasting with other studies ( Dhar et al., 2008),

MGO/high glucose did not show a strong pro-oxidant effect, as demonstrated by the ratings in the production BYL719 cell line of superoxide anion, hydrogen peroxide and nitric oxide. These results indicate which MGO/high glucose effects did not involve oxidative stress or calcium release. In addition, our study shows that the association of astaxanthin with vitamin C greatly improved neutrophil phagocytic capacity, decreasing all reactive oxygen species measured, pro-inflammatory IL-1β and TNF-α release, MPO activity and HClO production. The combination of astaxanthin with vitamin C alone has more antioxidant and anti-inflammatory than when they were in the presence of MGO/high glucose. The abnormal glucose homeostasis in diabetes due to the formation of the highly reactive metabolite MGO (Fleming et al., 2011, Tajima et al., 2002 and Thornalley, 2005) may be the key step in triggering the neutrophil dysfunction.

Neutrophils are the first immune cells to enter the site of infection or injury and there neutrophils kill microorganisms by ingesting them into phagocytic vacuoles (phagosomes). Therefore, phagocytosis is undoubtedly one of the most important roles of neutrophils. During phagocytosis, granules in the cytoplasm of neutrophils merge with the newly formed phagosome, forming the PIK3C2G phagolysosome (Kuijpers et al., 2001). The cytoplasmic granules of neutrophils have as one of their main constituent myeloperoxidase, the enzyme that catalyzes the reaction of hydrogen peroxide in the presence of halide ions such as chloride, bromide and iodide hipohalosos acids, in particular hypochlorous acid (Hampton et al., 1998 and Kettle et al., 1997). Hypochlorous acid is considered one of the most important anti-microbial agents produced by neutrophils. During phagocytosis there is activation of the NADPH oxidase, an enzyme complex that assembles in the phagosomal membrane and converts oxygen into the superoxide radical anion (O2 −). Superoxide anion is generated in the external surface (i.e.

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