Urinary Trypsin Inhibitor Attenuates Seawater-Induced Acute Lung Injury by Influencing the Activities of Nuclear Factor-ĸB and Its Related Inflammatory Mediators

Abstract

Background: Few data are available on the role of neutrophil elastase (NE) and nuclear factor-ĸB (NF-ĸB) in the course of seawater drowning-induced acute lung injury (SWD-ALI), and there is no evidence on the value of giving urinary trypsin inhibitor (UTI) in the case of SWD-ALI. Objective: To investigate the role of NF-ĸB and NE in the pathogenesis of SWD-ALI and whether UTI treatment can attenuate SWD-ALI in rabbits. Methods: Rabbits were randomly assigned to control, seawater drowning, and UTI treatment groups. The rabbits in the control group only suffered from intubation, whereas the rabbits in the seawater drowning group and the UTI treatment group received arterial injection of normal saline without/with 50,000 U/kg body weight of UTI after instillation of seawater into an endotracheal catheter. The activities or contents of NF-ĸB, MPO, NE, TNF-α, and IL-10 in lung tissue were measured by nonradioactive EMSA, biochemical methods, and ELISA, respectively. Results: After the seawater challenge, all of the rabbits demonstrated immediate drops in arterial PaO₂/FiO₂ and pronounced pulmonary edema and inflammatory cell infiltration with evidence of an increase in the ratio of wet weight to dry weight, lung permeability index, lung injury scores, and the activities or contents of NF-ĸB, NE, MPO, TNF-α, and IL-10. UTI treatment markedly attenuated lung histopathological changes with evidence of a decrease in all of the parameters, except for upregulation of IL-10. Arterial PaO₂/FiO₂ was significantly improved after 6 h of UTI treatment. Conclusion: These results suggest that NF-ĸB and NE play an important role in SWD-ALI. UTI protects against SWD-ALI, at least partly, through inhibition of the enhanced local activity of NF-ĸB, contents of TNF-α and NE, and infiltration of neutrophils and promotion of the level of IL-10.

Erythropoietin Pretreatment Attenuates Seawater Aspiration-Induced Acute Lung Injury in Rats

“…In addition, the excessive inflammatory response in seawater-induced ALI is characterized by the transmigration of neutrophils into the lung interstitial and the alveolar space, which in turn release numerous pro-inflammatory cytokines, such as TNF-α, IL-1β, and IL-6. Among the potent mediators, NF-κB pathway plays a pivotal role in the pro-inflammatory cytokines production in many inflammatory diseases and the activation of this pathway is also a crucial component in seawater aspiration-induced ALI [13,27]. It has been previously described that cytokines induced degradation of IkBs, which subsequently can induce NF-κB p65 and translocation from the cytoplasm to the nucleus where they bind with the target genes and regulate their transcription [5].…”

Ulinastatin for acute lung injury and acute respiratory distress syndrome: A systematic review and meta-analysis

“…It is reported that ulinastatin inhibits pathogenic changes in animal models of ALI/ARDS induced by many factors (including scald, seawater, LPS, phosgene) [6][7][8][9] . Immunoregulation and the mitigation of excessive inflammatory reaction might be involved.…”

Netrin-1 Promotes Epithelial Sodium Channel-Mediated Alveolar Fluid Clearance via Activation of the Adenosine 2B Receptor in Lipopolysaccharide-Induced Acute Lung Injury

“…The lung wet/dry weight (W/D) ratio was used to assess pulmonary edema [17,22]. Right lower lungs were isolated for determination of the W/D ratios.…”