Abstract
Treatment of acute respiratory distress syndrome (ARDS) is challenging due to its multifactorial aetiology. The benefit of antioxidant therapy was not consistently demonstrated by previous studies. We evaluated the effect of two different doses of intravenous (i.v.) N-acetylcysteine (NAC) on oxidative stress, inflammation and lung functions in the animal model of severe LPS-induced lung injury requiring mechanical ventilation. Adult Wistar rats with LPS (500 μg/kg; 2.2 mL/kg) were treated with i.v. NAC 10 mg/kg (NAC10) or 20 mg/kg (NAC20). Controls received saline. Lung functions, lung oedema, total white blood cell (WBC) count and neutrophils count in blood and bronchoalveolar lavage fluid, and tissue damage in homogenized lung were evaluated. NAC significantly improved ventilatory parameters and oxygenation, reduced lung oedema, WBC migration and alleviated oxidative stress and inflammation. NAC20 in comparison to NAC10 was more effective in reduction of oxidative damage of lipids and proteins, and inflammation almost to the baseline. In conclusion, LPS-instilled and mechanically ventilated rats may be a suitable model of ARDS to test the treatment effects at organ, systemic, cellular and molecular levels. The results together with literary data support the potential of NAC in ARDS.
Highlights
Acute respiratory distress syndrome (ARDS) is a common cause of respiratory failure in critically ill patients
Administration of LPS significantly deteriorated lung function expressed by ratio between partial pressure of oxygen in arterial blood to fraction of inspired oxygen (P/F), alveolar–arterial gradient (AaG), ventilation efficiency index (VEI) and oxygenation index (OI) in comparison to control group throughout the whole experiment
Both NAC therapies significantly improved P/F ratio, AaG, VEI and OI compared to LPS animals without treatment
Summary
Acute respiratory distress syndrome (ARDS) is a common cause of respiratory failure in critically ill patients. ARDS is characterized by rapid onset, and severe local followed by systemic inflammation, poor oxygenation, hypoxemia, increased alveolar-vascular permeability, lung oedema and pulmonary infiltrates [1,2]. Incidence of ARDS ranges from 6.3 to 7.2 cases/100,000 population/year and is associated with high morbidity and mortality [3,4,5]. ARDS is multifactorial syndrome and it is often modelled by lipopolysaccharide (LPS) administration in the lungs [6]. LPS, known as endotoxin, is a part of the outer membrane of Gram-negative bacteria and it has been previously used to induce ARDS in rodents [7,8]. In the respiratory system LPS binds to toll-like receptor (TLR) complex
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