This increase in ROS production was accompanied by an increase of damage in lipids and proteins (Table

1), whereas www.selleckchem.com/products/pci-32765.html catalase activity and GHS content were decreased. In an attempt to reduce the ROS production induced by the mixture of FA we added ASTA which resulted in a partial reduction of 20% (on average) in ROS production. Many antioxidants are particularly known to provide protection from ROS-mediated cellular damage. This effect is considered to be a defense mechanism against the attack of ROS. In addition, antioxidants have been linked to regulatory functions in cell growth, survival, cytotoxicity, and transformation possibly involving redox regulation and chemical toxicity (Larcombe et al., 2010). One mechanism to explain the increase in ROS production induced by FA could be by CAL101 the interaction of polyunsaturated, saturated and monounsaturated FA, which are present in our FA mixture, with components of the respiratory chain, thereby inhibiting the electron transport chain, when electrons are directly delivered to Complex III, e.g. from succinate. FA strongly enhance complex

III-associated superoxide anion generation (Schonfeld and Reiser, 2006 and Schonfeld and Wojtczak, 2007). Also, an elevation of intracellular Ca2+ induced by increased Ca2+ influx through voltage-gated Ca2+ channels caused by the FA mixture can stimulate mitochondrial generation of ROS. Moreover, Ca2+ via protein kinase C (PKC) activation enhances NADPH oxidase-dependent generation of ROS, and thus induces oxidative stress (Kruman et al., 1998, Morgan et al., 2007 and Yu et al., 2006). Interestingly, the high levels of ROS induced by FA were not totally inhibited by DPI (Fig. 3A), whereas in PMA-control group there was a reduction on

ROS production to basal levels. This phenomenon indicates that not only NADPH-oxidase is involved in ROS production of lymphocytes treated with FA. Furthermore, when SA was used as an electron transport chain inhibitor there was no reduction in ROS production induced by FA (Fig 3A). In summary, Quisqualic acid our data suggest that FA induces oxidative stress through increased production of superoxide anion, hydrogen peroxide and NO production, decreasing enzymatic activity of catalase and GSH content and increasing intracellular calcium concentration, which can be involved in increasing B-lymphocyte proliferation. Moreover, the increase in ROS and NO production explains the increase in lipid peroxidation and damage to cell proteins. Our data also show that ASTA can decrease the exacerbated production of ROS induced by FA, but only partially. Based on these results we can conclude that ASTA can partially prevent oxidative stress in human lymphocytes induced by a fatty acid mixture, probably by blenching/quenching free radical production.