Furthermore they claimed that AA-861 and zileuton are weak antioxidants that can serve as specific tools

However, consistent with the findings obtained from the TUNEL and hematoxylin and eosin staining, PAF administration prevented apoptosis in these cells. Finally, no apparent apoptosis was observed in the spleen of mice administered with PAF alone. This study demonstrated the protective effect of exogenous PAF administration against LPS-induced endotoxemia and identified the molecular mechanisms involved in this biological process. Contrary to previous pharmacologic reports concerning the role of PAF in inflammation, our results demonstrate that mice treated with PAF ON-014185 acquired resistance to LPS-induced endotoxic shock, and that this effect can be blocked by the PAF-R antagonist BN-52021. Although no therapeutic activity was observed until PAF treatment was delayed to 6 h after LPS challenge, treatment with PAF before or immediately after a lethal LPS dose protected mice against endotoxic death. These results challenge the current paradigm of PAF as an important mediator of sepsis, which is based on the concept that septic shock results from an uncontrolled inflammatory response. For many years, studies on the biological effects of PAF as a potent inflammatory mediator were mainly been focused on the activation of cells involved in inflammation. Thus, many clinical trials for severe NVP-LBH589 customer reviews sepsis attempted to inhibit the action of PAF with a variety of PAF-R antagonists. Although septic animal models exhibit beneficial effects as a result of PAF antagonist treatment, clinical studies on patients with sepsis do not display similar outcome. Because the dose of PAF-R antagonists which inhibit endotoxin-induced sepsis are typically more than 10-fold higher than those for PAF released during sepsis, it is suggests that protective effect of PAF antagonist may be related in non-specific inhibition. Study using PAF-R deficient mice further verified these points. Ishii S et al observed no significant differences in lethality and production of inflammatory cytokines during endotoxic shock between wild-type and PAF-R-deficient mice, implying that PAF is not essential for endotoxic shock development. Recently, Walterscheid et al provided evidence for a novel immunoreglatory role for PAF, which, in addition to b