Although nitrated proteins have been repeatedly used as markers of lung injury, little is known about their formation and metabolism under hyperoxia. We therefore measured 3-nitrotyrosine (3NTYR) concentrations in lung tissue and serum of rats with carrageenan-induced pneumonia exposed to hyperoxia. Twenty-nine Wistar male rats were assigned to one of 4 groups. Two experimental groups were treated by intratracheal application of carrageenan (0.5 ml of 0.7 % solution) and then one was exposed to hyperoxia for 7 days (FIO2 0.8), the other to air. Rats of two control groups breathed either hyperoxic gas mixture or air for 7 days. At the end of exposure the ventilation was determined in anesthetized, intubated animals in which 3NTYR concentrations were measured in the lung tissue and nitrites and nitrates (NOx) were estimated in the serum. Carrageenan instillation increased 3NTYR concentrations in lung tissue (carrageenan-normoxic group 147±7 pmol/g protein, control 90±10 pmol/g protein) and NOx concentration in the serum (carrageenan-normoxic group 126±13 ppb, control 78±9 ppb). Hyperoxia had no effect on lung tissue 3NTYR concentration in controls (control-hyperoxic 100±14 pmol/g protein) but blocked the increase of lung tissue 3NTYR in carrageenan-treated rats (carrageenan-hyperoxic 82±13 pmol/g protein), increased NOx in serum (control-hyperoxic 127±19 ppb) and decreased serum concentration of 3NTYR in both hyperoxic groups (carrageenan-hyperoxic 51±5 pmol/g protein, control-hyperoxic 67±7 pmol/g protein, carrageenan-normoxic 82±9 pmol/g protein, control 91±7 pmol/g protein). The results suggest that hyperoxia affects nitration of tyrosine residues, probably by increasing 3NTYR degradation.
A common problem in management of polytrauma – a simultaneous injury to more than one organ or organ system, at least one of them lethal without intervention – is a discrepancy between a relatively good initial state and a serious subsequent development. Since nitric oxide (NO) is produced in high quantities during tissue injury, we assumed that serum levels of NO (and its oxidation products, NOx) might serve as a prognostic marker of polytrauma severity. However, we found recently that NOx was increased in polytrauma, but not in the most severe cases. The present study was undertaken to test the hypothesis that serum NOx is reduced in severe polytrauma by concomitant overproduction of reactive oxygen species (ROS). Polytrauma was induced in rats under anesthesia by bilateral fracture of femurs and tibiae plus incision of the right liver lobe through
laparotomy. Serum NOx was measured by chemiluminescence after hot acidic reduction. The role of ROS was assessed by treatment with an antioxidant, N-acetyl-L-cysteine (NAC). Experimental polytrauma elevated NOx from 11.0±0.7 to 23.8±4.5 ppb. This was completely prevented by NAC treatment (9.1±2.2 ppb). Serum NOx is elevated in severe polytrauma, and this is not reduced by ROS. On the contrary, ROS are necessary for the NOx elevation, probably because ROS produced by inflammatory cells activated by the polytrauma induce massive NO production.