Biochemical markers of pulmonary oxygen toxicity
This study has investigated potential biochemical markers of pulmonary oxygen toxicity (POT). Toxicity was investigated in male Sprague Dawley rats exposed to oxygen partial pressures ranging from 0.21-2.5 bars. It is known that prolonged exposure to 1 bar of oxygen damages pulmonary endothelial cells and so the biochemical functions of these cells have been studied. Control isolated perfused rat lungs were able to clear and/or metabolise a wide range of substances including 5-HT, PGE2, bradykinin, and angiotensin 1, all endothelial cell functions. As expected 5-HT clearance was compromised in isolated perfused rat lung obtained from rats exposed to 1 bar of oxygen, confirming endothelial cell damage. However the clearance of 5-HT by lungs obtained from rats exposed to 2.5 bars was normal, implying that the site of toxicity is different at these partial pressures. In addition enhancement of toxicity by vitamin E deficiency was not associated with endothelial cell damage at 2.5 bar. At the molecular level oxygen free radicals are thought to be the causative agents of POT. The radicals are reputed to damage lipids, but a process of peroxidation. One of the lipid fragment products of ω6 polyunsaturated fatty acids is n-pentane, a compound which is excreted on the breath. Monitoring of this compound during exposure to 0.21, 1.0, 2.5 bars of oxygen even in vitamin E deficient rats did not show a rise in pentane expiration in response to oxygen exposure. This implies that peroxidation of ω6 polyunsaturated fatty acids did not take place, although other lipids may have been peroxidised. In conclusion the site of POT may depend on the partial pressure of oxygen. Endothelial cell damage is probably absent during exposure to 2.5 bars of oxygen. In addition n-pentane monitoring, a reputed marker of POT, failed to reveal lipid perodixation during exposure to hyperoxia.