oxytocin and Acute-Lung-Injury

Although several studies demonstrate the anti-inflammatory effect of oxytocin in different pathophysiological processes, there are limited data describing the impact of oxytocin on acute respiratory distress syndrome (ARDS). We aimed to elucidate the protective effect of oxytocin in ARDS with histopathological evaluation and radiological imaging in addition to biochemical markers.. Fecal intraperitoneal injection procedure (FIP) was performed on 24 of 32 rats included in the study for creating a sepsis model. Rats were randomly assigned into four groups: control group (no procedure was applied, n = 8), untreated septic group [was operated (FIP) and received no treatment, n = 8], placebo group (FIP, treated with 10 ml/kg of saline at once, n = 8), and treated group (FIP, treated with 0.1 mg/kg of oxytocin at once, n = 8). Chest CT was performed for all rats 20 hours after the procedure and density of the lungs were measured manually by using HU. All animals were sacrificed for histopathological examination of lung damage and blood samples were collected for biochemical analysis.. Plasma malondialdehyde (MDA), lactic acid (LA), C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), interleukin 1-beta (IL 1-β) levels were significantly increased in the placebo (FIP + saline) and the untreated (FIP) groups, and plasma levels of all biomarkers were reversed by oxytocin. Further, the density of the lung parenchyma (Hounsfield unit) on CT images and the histopathological lung damage score values were closer to the control group in the oxytocin-treated group compared to the placebo group.. Our findings suggested that oxytocin could exert anti-inflammatory, antioxidant and protective effects in FIP-induced ARDS.

Topics: Acute Lung Injury; Animals; Anti-Inflammatory Agents; Antioxidants; Lung; Oxytocin; Rats; Sepsis; Tomography, X-Ray Computed; Tumor Necrosis Factor-alpha

Oxytocin (OT) has been reported to have a protective effect in lipopolysaccharide-induced experimental acute lung injury (ALI). However, its role in heat stroke-related ALI has never been investigated. Herein, we aimed to explore the therapeutic effects and potential mechanism of action of OT on heat-induced ALI. Rats were treated with OT 60 min before the start of heat stress (42 °C for 80 min). Twenty minutes after the termination of heat stress, the effects of OT on lung histopathological changes, edema, acute pleurisy and the bronchoalveolar fluid levels of inflammatory cytokines and indicators of ischemia, cellular damage, and oxidative damage were assessed. We also evaluated the influence of OT pretreatment on heat-induced hypotension, hyperthermia, ALI score, and death in a rat model of heat stroke. The results showed that OT significantly reduced heat-induced lung edema, neutrophil infiltration, hemorrhage score, myeloperoxidase activity, ischemia, and the levels of inflammatory and oxidative damage markers in bronchoalveolar lavage fluid. The survival assessment confirmed the pathophysiological and biochemical results. An OT receptor antagonist (L-368,899) was administered 10 min before the OT injection to further demonstrate the role of OT in heat-induced ALI. The results showed that OT could not protect against the aforementioned heat stroke responses in rats treated with L-368,899. Interestingly, OT treatment 80 min after the start of heat shock did not affect survival. In conclusion, our data indicate that OT pretreatment can reduce the ischemic, inflammatory and oxidative responses related to heat-induced ALI in rats.

Topics: Acute Lung Injury; Animals; Bronchoalveolar Lavage Fluid; Camphanes; Cytokines; Disease Models, Animal; Fever; Heat Stroke; Heat-Shock Response; Hypotension; Lung; Male; Neutrophil Infiltration; Oxytocin; Peroxidase; Piperazines; Protective Agents; Pulmonary Edema; Rats; Rats, Sprague-Dawley; Receptors, Oxytocin; Survival Analysis

Oxytocin (OT), a neurohypophyseal hormone synthesized in the paraventricular and supraoptic nuclei of the hypothalamus, has been reported to have an anti- inflammatory effect. However, its role in acute lung injury (ALI) has never been investigated. The aim of this study was to explore the therapeutic effects and potential mechanism action of OT on lipopolysaccharide (LPS)-induced ALI. Mice were treated with OT 30 min before the intraperitoneal injection of LPS. After 2 h, the effects of OT on lung histopathological changes, lung wet/dry (W/D) ratio, myeloperoxidase (MPO) activity, levels of inflammatory cytokines in the bronchoalveolar lavage fluid (BALF), and expression of inflammation proteins were detected. The results showed that OT significantly reduced LPS-induced pathological injury, W/D ratio, MPO activity, and the levels of interleukin (IL)-1β, IL-18 and IL-6. Further, OT also inhibited LPS-induced Toll-like receptor 4 expression and NLR family pyrin domain containing 3 inflammasome activation. OT receptor antagonist (L-368,899) was given 90 min before injecting OT to further demonstrate the role of OT in LPS-induced ALI. The results showed OT could not alleviate the aforementioned inflammatory reactions after administering L-368,899. In conclusion, the present results indicated that OT could reduce inflammatory responses of LPS-induced ALI.

Topics: Acute Lung Injury; Animals; Anti-Inflammatory Agents; Cytokines; Inflammation; Lipopolysaccharides; Male; Mice; Mice, Inbred C57BL; Oxytocin

Acute lung injury (ALI) is one of the leading causes of death in sepsis. Endothelial inflammation and dysfunction play a prominent role in development of ALI. Glycolysis is the predominant bioenergetic pathway for endothelial cells (ECs). However, the role of EC glycolysis in ALI of sepsis remains unclear. Here we show that both the expression and activity of PFKFB3, a key glycolytic activator, were markedly increased in lipopolysaccharide (LPS)-treated human pulmonary arterial ECs (HPAECs) in vitro and in lung ECs of mice challenged with LPS in vivo. PFKFB3 knockdown significantly reduced LPS-enhanced glycolysis in HPAECs. Compared with LPS-challenged wild-type mice, endothelial-specific Pfkfb3 knockout (Pfkfb3

Topics: Acute Lung Injury; Animals; Disease Models, Animal; Endothelial Cells; Endothelium, Vascular; Endotoxemia; Glycolysis; Humans; Inflammation; Intercellular Adhesion Molecule-1; Lipopolysaccharides; Lung; Mice; Monocytes; NF-kappa B; Oxytocin; Phosphofructokinase-2; Pulmonary Edema; Sepsis; Signal Transduction; Vascular Cell Adhesion Molecule-1