Oxidant stress and essential fatty acids in patients with risk and established ARDS
Introduction
The acute respiratory distress syndrome (ARDS) develops when the lung is injured. This can occur by a variety of processes including sepsis, major trauma, pancreatitis or aspiration of gastric content. Dyspnea, hypoxia and diffuse pulmonary infiltrates on the chest radiograph [1] characterize ARDS. It is associated with development of diffuse pulmonary cell injury, interstitial and alveolar edema and inflammation [2]. Recent investigations into the etiologic mechanisms of ARDS have examined the role of variety of humoral mediators including oxygen free radicals, arachidonic acid metabolites and cytokines. Free radicals produced by stimulated neutrophils may be the mediators of pulmonary injury [3], [4]. Aggregates of activated leukocytes in the pulmonary microvasculature release free oxygen radicals [5] that are able to attack the polyunsaturated fatty acid (PUFA) chain of membrane lipids, thus initiating a peroxidation process. Peroxidation leads to loss of the functional integrity of the cell membranes, culminating in acute increase of alveolar-capillary permeability.
Dietary linoleic acid (18:2n6) and alpha-linolenic acid (ALA, 18:3n3) are essential fatty acids (EFAs) that are metabolized by a series of desaturases and elongases to form arachidonic acid (AA, 20:4n6) and eicosapentaenoic acid (20:5n3), respectively which are precursors of the 2 and 3 series of eicosanoids, whereas dihomo-gamma-linolenic acid (DGLA, 20:3n6) is metabolized to eicosanoids of the 1 series. There is evidence that DGLA and its products and EPA and its products can decrease leukocyte chemotaxis, leukotriene production and suppression of inflammation [6]. Several studies have demonstrated that the circulations of polyunsaturated fatty acids were altered in various diseased states such as septicemia [7], rheumatoid arthritis, pneumonia [8], hypertension [9]. These studies indicate that the patients who are at risk of developing ARDS and patients with established ARDS may have altered oxidative stress and fatty acid metabolism. Hence, we studied the plasma concentrations of polyunsaturated fatty acids (PUFA), lipid peroxides and nitric oxide, in patients who are at risk of ARDS and those with established ARDS.
Section snippets
Materials and methods
Patients admitted to the emergency medicine department and the respiratory intensive care unit of our hospital, and who were at risk or had a diagnosis of ARDS were included in the study. The criteria for defining patients at risk included polytrauma, suspected fat embolism, septic syndrome, aspiration of gastric contents, and pancreatitis [10] and criteria to define established ARDS were as defined by Murray et al. [11] i.e., lung injury score, 0.1 to 2.5 (mild to moderate ARDS), >2.5
Results
The results given in Fig. 1 suggest that there is a significant increase in the production of free radicals, as evidenced by increased lipid peroxidation products in patients at risk as well as those with established ARDS. The amount of lipid peroxidation products in established ARDS were significantly higher when compared to patients who are at risk. The levels of nitric oxide (measured as its stable metabolite, nitrite) were significantly low in patients with established ARDS compared to
Discussion
Acute lung injury results from a complex interplay between the damaging effects of reactive oxygen species generated by alveolar, vascular, inflammatory cells and humoral mediators such as cell growth factors [19]. Histological and laboratory data indicate that progress of fibroproliferation in the ARDS is associated with persistent inflammation in lung and accumulation of neutrophils [20]. The main source of reactive oxygen species (ROI) in lung is NADPH oxidase of phagocyte cells [21].
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