Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
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Administration of melatonin is hepatoprotective in various experimental models of stress; the mechanism of action can be attributed to antioxidant effects. While melatonin reduces hepatocellular injury after oxidative stress in animal models, this effect cannot be observed in human hepatocellular carcinoma cells (HepG2). This study was designed to test the hypothesis that melatonin may influence viability of primary hepatocytes (PH) under oxidative stress. ⋯ : Melatonin pretreatment increases viability of PH but not of HepG2 cells under oxidative stress. This model of melatonin responsive (PH) and melatonin unresponsive (HepG2) cells will allow us to characterize the molecular pattern of melatonins protective effects under oxidative stress.
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Intestinal ischemia-reperfusion (I/R) injury can occur in clinical settings such as organ transplantation, cardiopulmonary bypass and trauma. The noble gas helium attenuates I/R injury in a number of animal organs and thus may offer a strategy for reducing I/R-induced intestinal injury in clinical settings. In the present study, we used four different helium preconditioning (HPC) profiles to investigate the potential beneficial effect of HPC on I/R-induced intestinal injury. ⋯ The results showed that the HPC profile consisting of three cycles of 10 or 15 min of helium breathing and three cycles of 5 min of air breathing reduced I/R-induced intestinal injury, cell apoptosis, and the inflammatory response. However, the 2- or 5-min helium breathing did not confer any protective effects. It seems that longer helium episodes should be used in HPC profiles designed to attenuate intestinal I/R injury.
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Acute lung injury (ALI) is characterized by lung inflammation and diffuse infiltration of neutrophils. Neutrophil apoptosis is recognized as an important control point in the resolution of inflammation. Maresin 1 (MaR1) is a new docosahexaenoic acid-derived proresolving agent that promotes the resolution of inflammation. ⋯ Moreover, MaR1 also reduced the LPS-induced production of proinflammatory cytokines and upregulated the production of the anti-inflammatory cytokine interleukin-10. In contrast, treatment with z-VAD-fmk inhibited the proapoptotic action of MaR1 and attenuated the protective effects of MaR1 in LPS-induced ALI. Taken together, MaR1 promotes the resolution of LPS-induced ALI by overcoming LPS-mediated suppression of neutrophil apoptosis.
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Polytrauma patients are at high risk for opportunistic infections due to the development of immunosuppression. During bacterial infections, the synthesis of Interleukin (IL) 12 triggers Natural Killer (NK) cells for the release of Interferon (IFN) gamma that stimulates phagocytes for the eradication of the pathogens. ⋯ The suppressed NK cell function after severe injury is associated with disturbed IL-12 signal transduction and might contribute to the increased susceptibility to infections after polytrauma.
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SIRS (systemic inflammatory response syndrome) and sepsis are associated with increased oxidative stress. Oxidative stress activates endothelia, leads to adherence of leukocytes and induces oxidative modifications in membranes by lipid peroxidation. Biliverdin reductase (BVR) and heme oxygenase (HO) are important for the prevention of oxidative stress, activation of endothelial cells and leucocyte adherence. The cytoprotective effects of HO and BVR are supposed to be mediated by heme degradation products such as biliverdin (BV) and bilirubin (BR) forming a potent endogenous anti-oxidative system. Aim of the study was to investigate whether sepsis or SIRS lead to increased lipid peroxidation that associate with changes in the activity of BVR of human leukocytes. ⋯ The dynamics of BVR activity in leukocytes in the early stages of SIRS and sepsis patients suggest that leukocytes may contribute via increased recycling of BR to the anti-oxidative and anti-inflammatory defence. Supported by EU-ESF and NSRF-THALES.