4-hydroxy-2-nonenal and Pleural-Effusion

The pleural cavity is normally in a state of negative pressure and low oxygen tension. It is exposed to the atmosphere during thoracic surgery. However, no reports of pathophysiological investigation of the effects of pleural oxygen exposure involved in thoracotomy are available. In this study, the effects of pleural oxygen exposure on systemic and pleural inflammation were investigated. Male Wistar rats (9 weeks old) were placed on mechanical ventilation and underwent thoracotomy with lipopolysaccharide (LPS) administration, which simulates latent inflammatory condition. The pleural cavity was exposed to nitrogen (N(2) thoracotomy group), air (20% oxygen, air thoracotomy group), or 100% oxygen (O(2) thoracotomy group) under mechanical ventilation for 2 h. Animals were sacrificed 2 h or 8 h after LPS administration, and inflammatory indices (plasma tumor necrosis factor-alpha and interleukin-6, histology) were examined. For examination of inflammatory mediators, pleural effusion was added to cultured RAW264 cells, a murine macrophage cell line, and tumor necrosis factor-alpha levels in supernatant were measured. The capacity of pleural superoxide generation was investigated without LPS administration. Results showed increases in plasma interleukin-6 concentration and lung injury in the air and O(2) thoracotomy groups. Pleural oxygen exposure stimulated pleural superoxide generation, and increased pleural 4-hydroxy-2-nonenal and lung lipid peroxide concentrations. Tumor necrosis factor-alpha levels in cell culture supernatants were increased by the addition of pleural effusion from the air and O(2) thoracotomy groups. In conclusion, pleural oxygen exposure induced pleural oxidative injury and aggravated latent systemic inflammatory response.

Topics: Aldehydes; Animals; Cell Line; Culture Media, Conditioned; Inflammation; Interleukin-6; Lipid Peroxides; Lipopolysaccharides; Lung; Macrophages; Male; Mice; Oxidative Stress; Oxygen; Pleura; Pleural Effusion; Rats; Rats, Wistar; Respiration, Artificial; Superoxides; Thoracotomy; Tumor Necrosis Factor-alpha

Previous studies showed that the lipid peroxidation product 4-hydroxy-trans-2-nonenal (HNE) stimulates the rat neutrophil oriented migration in vitro within a micromolar range. Its effect is weak with respect to other known chemoattractants, but highly significant on the basis of a two-way analysis of variance. Other hydroxyalkenals were found to be chemotactic within a pico-micromolar range, and their chemotactic power was not correlated to their lipophilicity. The structural requirements for the chemotactic activity of the hydroxyalkenals were studied by testing the influence of alkanals and 2-alkenals on oriented migration. Alkanals are lacking both the trans double-bond and the hydroxy group, while 2-alkenals are lacking only the hydroxy group. The 2-alkenals (2-octenal, 2-nonenal) were found to be chemotactic, whereas alkanals (hexanal, octanal, nonanal) were ineffective. Therefore the chemotactic activity of the aliphatic aldehydes is dependent on the -C = C-CHO part of their molecule. The possibility that unsaturated aliphatic aldehydes are present in an inflammatory site at a concentration at which they are chemotactic in vitro was also investigated. Carbonyls in pleural exudates were analysed at different times after a pleurisy induction and HNE was detected both in the cells and in the cell-free supernant of the exudate at increasing concentrations during the 4 hours of the experiment. The exact source of HNE is unknown, but since HNE has been identified among the degradation products of peroxidized lipids it is likely that this aldehyde is formed consequent on lipid peroxidation reactions which occur at the phlogistic site. The possibility that HNE is involved, at least in part, in the recruitment of neutrophils in the inflammatory area is suggested.

Topics: Aldehydes; Analysis of Variance; Animals; Cell Movement; Cell Survival; Chemotactic Factors; Chemotaxis, Leukocyte; Chromatography, High Pressure Liquid; Lipid Peroxides; Male; Neutrophils; Pleural Effusion; Rats; Rats, Inbred Strains