allopurinol and Systemic-Inflammatory-Response-Syndrome

Endotoxin is a potent microbial mediator implicated in sepsis. We investigated the anti-inflammatory effect of leaf essential oil from Cinnamomum osmophloeum Kanehira (CO) of the linalool chemotype on endotoxin-injected mice. Mice were administered CO or vehicle by gavage before endotoxin injection and were killed 12 h after injection. Neither growth nor the organ weight or tissue weight to body weight ratio was affected by CO treatment. CO significantly lowered peripheral levels of tumor necrosis factor-α, interleukin (IL)-1β, IL-18, interferon-γ, and nitric oxide and inhibited the expression of toll-like receptor 4 (TLR4), myeloid differentiation primary response gene (88), myeloid differentiation factor 2, apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC), caspase-1, and Nod-like receptor family, pyrin domain containing 3 (NLRP3). CO also inhibited the activation of nuclear factor-ĸB, inhibited the activity of caspase-1 in small intestine, and ameliorated intestinal edema. Our data provide strong evidence for a protective effect of CO of the linalool chemotype in the endotoxin-induced systemic inflammatory response in close association with suppression of the TLR4 and NLRP3 signaling pathways in intestine.

Topics: Animals; Anti-Inflammatory Agents; Body Weight; Carrier Proteins; Cinnamomum; Cytokines; Disease Models, Animal; Endotoxins; Ileum; Inflammation Mediators; Intestinal Mucosa; Intestines; Lymph Nodes; Male; Mesentery; Mice; NF-kappa B; Nitrates; Nitrites; NLR Family, Pyrin Domain-Containing 3 Protein; Oils, Volatile; Organ Size; Plant Leaves; Protective Agents; Signal Transduction; Systemic Inflammatory Response Syndrome; Toll-Like Receptor 4; Xanthine Oxidase

The possible role of xanthine oxidase (XO) activation in the signal transduction process during the septic shock syndrome was examined. The XO activity index after caffeine intake was assessed simultaneously with the blood glutathione redox ratio, a known parameter of oxidative stress.. An investigational clinical study in a nine-bed pediatric intensive care unit.. Critically ill infants and children (n = 34) with systemic inflammatory response syndrome following infection, trauma or major surgery. Biochemical investigations (n = 54) were performed at various stages of the shock syndrome, characterized by pediatric risk of mortality and organ dysmetabolic scores. Controls consisted of 30 healthy children.. The in vivo XO activity index was measured as the urinary ratio of two metabolites of caffeine: 1-methyluric acid and 1-methylxanthine. The blood concentrations of oxidized (GSSG) and reduced glutathione (GSH) were determined. The XO activity index and redox ratio GSSG/GSH were highly increased in patients in shock dominated by the clinical symptoms of a proinflammatory response. A significantly lower XO activity index was found with an increased GSSG/ GSH in patients whose stage of shock was characteristic of an excessive anti-inflammatory response. The XO activity index and GSSG/ GSH were correlated closely with each other (r = 0.624, n = 54; p < 0.001), and were also related to the daily severity scores.. Potent and simultaneous activation of the two redox systems strongly indicates a definite role of free radicals from XO in the overspill of the acute proinflammatory reaction of the shock syndrome, followed by a significant downregulation.

Topics: Biomarkers; Case-Control Studies; Child; Child, Preschool; Female; Glutathione; Humans; Infant; Male; Multiple Organ Failure; Oxidation-Reduction; Oxidative Stress; Statistics, Nonparametric; Systemic Inflammatory Response Syndrome; Xanthine Oxidase

Thermal trauma has a direct effect on mast cells, triggering the secretion of histamine. This secretion leads to an enhanced xanthine oxidase activity and an increased production of reactive oxygen species (ROS), the latter being produced after burns through differing mechanisms. As ROS have been shown to have deleterious effects on cellular membranes, a lesion of the mast cell membrane could close the circle of autoinjury due to the vasoactive actions of mast cell mediators. Our studies were designed to assess the potentiality of ROS as stimulators of mast cell degranulation after burns by comparing two groups of rats treated, respectively, with SOD and saline solution after a scald injury. Plasma levels of tryptase and histamine were analyzed as markers of mast cell activity. A comparison of the mean increases of tryptase between baseline and 3-h postburn levels in the two groups shows significant differences (p < 0.001) (control: 0.13+/-0.04, SOD: 0.03+/-0.01). When comparing the mean increases between the baseline and 3 h postburn levels of histamine in the two groups, significant differences were also found (p < 0.001) (control group: 2.70+/-0.57. SOD group: 1.22+/-0.32). The lower levels of histamine and tryptase induced by SOD provides indirect evidence that ROS are involved in the process, causing the release of such mediators by mast cells, which may in turn suggest that ROS can act as stimulators of mast cell degranulation in burns.

Topics: Animals; Biomarkers; Burns; Cell Degranulation; Chymases; Disease Models, Animal; Histamine; Male; Mast Cells; Rats; Rats, Wistar; Reactive Oxygen Species; Serine Endopeptidases; Superoxide Dismutase; Systemic Inflammatory Response Syndrome; Tryptases; Xanthine Oxidase

To determine xanthine oxidase activity, free radical concentrations, and lipid peroxidation in patients with sepsis syndrome compared with noninfected critically ill patients.. A prospective observational study.. A nine-bed intensive care unit in a university teaching hospital trust.. Fourteen consecutive patients who met the established criteria for sepsis syndrome with multiple organ dysfunction syndrome, and ten noninfected critically ill patients were studied.. None.. Xanthine oxidase activity was increased in septic patients compared with both healthy volunteers (p < .01) and noninfected patients (p < .05), and was highest in the six patients who survived (p < .05). Lipid peroxides were increased in both septic patients (p < .001) and nonseptic controls (p < .001). Xanthine oxidase activity did not relate to the Acute Physiology and Chronic Health Evaluation (APACHE) II score or to the presence of organ dysfunction. The mean ascorbyl radical concentration (arbitrary units) determined by electron paramagnetic resonance following spin trapping was increased in patients compared with healthy subjects (p < .05).. Patients with sepsis have xanthine oxidase activation, high free-radical concentrations, and evidence of free radical damage. The finding that xanthine oxidase activity was lower in those patients who died, coupled with increased lactate concentrations implies more severe ischemia with incomplete reperfusion resulting in less xanthine oxidase "wash out" into the circulation. Increased ascorbyl radical concentrations may be due to an increased radical generation and oxidant scavenging, but appears to be unrelated to xanthine oxidase activity within the circulation.

Topics: Adult; Aged; Aged, 80 and over; APACHE; Critical Illness; Female; Free Radicals; Humans; Lactates; Lipid Peroxidation; Male; Middle Aged; Multiple Organ Failure; Prospective Studies; Survival Rate; Systemic Inflammatory Response Syndrome; Xanthine Oxidase