Abstract
Sepsis leads to systemic hypotension, disturbed perfusion, inflammation, and tissue toxicity in vital organs. Neuropeptide W (NPW) has modulatory effects in the control of blood pressure and inflammatory processes, implicating a potential beneficial effect against sepsis-induced oxidative damage. Under anesthesia, male Sprague Dawley rats underwent cecal ligation and puncture. Immediately after surgery, either saline or TNF-alpha inhibitor (etanercept; 1 mg/kg) antibiotic (ceftriaxon; 10 mg/kg) combination or NPW (0.1, 1, or 3 μg/kg) was given subcutaneously, and injections were repeated on the 12thand 24thh. The sham-operated control group was treated with saline at the same time points. All rats were euthanized on the 25thh of surgery. Sepsis resulted in oxidative damage of the brain, heart, lung, liver, and kidney. Elevations in blood urea nitrogen and alkaline phosphatase, showing renal and hepatic dysfunction, were not evident when septic rats were treated with NPW. NPW reduced serum levels of C-reactive protein, corticosterone, and interleukin-6, while histopathologically verified tissue damage in all the studied tissues was ameliorated. NPW treatment suppressed lipid peroxidation in the heart, lung, and brain, and the depleted antioxidant GSH levels of the brain and heart were replenished by NPW. Moreover, sepsis-related neutrophil recruitment to the liver and lung was also suppressed by NPW. Although the survival rate of the rats was not significantly prolonged by NPW, most of these improvements in systemic and local inflammatory events were comparable with those reached by the etanercept and antibiotic combination, suggesting the therapeutic impact of NPW during the acute period of sepsis.
Highlights
Sepsis was recently redefined as a syndrome presenting with “life-threatening organ dysfunction due to dysregulated response of the host to infection” [1]
Multi-organ dysfunction in sepsis is characterized by the infiltration of leukocytes into the target tissues, enhanced generation of reactive oxygen species (ROS) and activation of several pro-inflammatory cytokines, all of which lead to lipid peroxidation, DNA damage and the resultant oxidative organ damage [6, 7]
Serum pro-calcitonin levels measured at the 25th h of the sepsis induction showed a tendency to increase, but no statistically significant difference was observed among the experimental groups (Table 2)
Summary
Sepsis was recently redefined as a syndrome presenting with “life-threatening organ dysfunction due to dysregulated response of the host to infection” [1]. Despite the ongoing advances in monitoring, medical treatment and supportive care, sepsis still keeps its leading position as the cause of mortality in intensive care units and it remains accountable for the highest healthcare costs in the world [1, 2]. Independent of the source of the infection, sepsis can lead to systemic hypotension and inflammation, which together yield to disturbed perfusion and tissue toxicity in several vital organs [4]. Multi-organ dysfunction in sepsis is characterized by the infiltration of leukocytes into the target tissues, enhanced generation of reactive oxygen species (ROS) and activation of several pro-inflammatory cytokines, all of which lead to lipid peroxidation, DNA damage and the resultant oxidative organ damage [6, 7]. Apart from the treatment strategies based on initial fluid resuscitation, anti-endotoxins, vasopressors and antibiotics [13, 14], no effective treatments for sepsis have been introduced yet, indicating the ongoing need for the development of novel treatment choices
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