The therapeutic efficacy of Ulinastatin for rats with smoking inhalation injury

Abstract

Smoke inhalation injury represents a major cause of mortality in burn patients and is associated with a high incidence of pulmonary complications. Ulinastatin (UTI) has been widely used as a drug for patients with severe burn, sepsis, severe acute pancreatitis, and multiple organ dysfunction syndrome. In view of the critical role of inflammatory response in pathogenesis of smoke inhalation-induced lung injury and the anti-inflammatory effects of UTI, we hypothesized that treatment with UTI could lessen smoke inhalation-induced lung injury. In this study, fifty-four rats were equally randomized to three groups: Sham group (ambient air inhalation), Control group (smoke inhalation injury) and UTI treatment group (UTI treatment plus smoke inhalation injury). At sampling, bronchoalveolar lavage fluid was performed to determine total protein concentration and pro-inflammatory cytokine levels. Lung tissues were collected for the measurement of wet/dry ratio, myeloperoxidase, histopathology, hydroxyproline, collagens I and III, and western blotting. Our present work exhibited that UTI attenuated the lung histopathological alterations, improved the pulmonary function, inhibited neutrophil accumulation and mitigated pulmonary edema. In addition, UTI mitigated the inflammatory response, and further prevented the initiation of downstream inflammatory cascades: NF-κB and p-JNK. Importantly, UTI also mitigated smoke inhalation-induced pulmonary fibrosis as evidenced by Masson-Goldner trichrome staining with the content of hydroxyproline and collagens I and III. In conclusion, our data demonstrated that UTI protected rat against smoke inhalation-induced acute lung injury and the subsequent development of pulmonary fibrosis.

Ulinastatin activates haem oxygenase 1 antioxidant pathway and attenuates allergic inflammation

“…The second finding of this study is that UTI is also an effective anti‐inflammatory agent against allergic inflammation. Previous studies have reported that UTI protected against neutrophil‐mediated inflammation and organ injury (Masuda et al ., ; Inoue et al ., 2005a,b; Molor‐Erdene et al ., ; Takano et al ., ; Koga et al ., ; Qiu et al ., ; Rui et al ., ). However, the effect of UTI on allergic inflammation has not been studied.…”

“…Exogenous administration of UTI to endotoxaemic animals inhibited inflammatory mediator production, reversed systemic hypotension (Molor‐Erdene et al ., ), prevented intravascular coagulation (Takano et al ., ) and ameliorated multiple organ injury (Takano et al ., ; Zhang et al ., ). UTI protected against ischaemia‐reperfusion (Yano et al ., ; Koga et al ., ), haemorrhage (Masuda et al ., ), smoke inhalation (Qiu et al ., ) or organ injury induced by sea water inhalation (Rui et al ., ). UTI has also been shown to have beneficial effects in patients with severe sepsis, traumatic brain injury and acute Kawasaki disease (Chen et al ., ; Kanai et al ., ; Tu et al ., ).…”

Hydrostatin-SN1, a Sea Snake-Derived Bioactive Peptide, Reduces Inflammation in a Mouse Model of Acute Lung Injury

“…The activation of NF-κB is regulated via cytoplasmic sequestration of NF-κB by the inhibitor of κB (IκBs) family of proteins (Qiu et al, 2012). IκB-α, one isoform of IκBs, can sequester NF-κB in the cytoplasm.…”

Puerarin attenuates smoke inhalation injury by regulation of Th1/Th2 expression and inhibition of Th17 cells in rats

“…In contrast, puerarin could attenuate pathological changes and protect rats against immune-mediated lung injury. As a histological hallmark of ALI/ARDS, local accumulation of neutrophils in lung parenchyma is implicated in the pathophysiology of ALI induced by smoke inhalation, lipopolysaccharide, radiation and ischemiareperfusion injury; and investigation of BALF from patients with ARDS has shown excess numbers of neutrophils, which produce excessive amounts of pathogenic factors such as protease and elastase [19,[23][24][25]. Consistent with previous studies, our results showed that neutrophils were significantly increased in BALF after smoke inhalation, but were decreased by administration of puerarin.…”