thiourea and Hyperoxia

Aquaporin (AQP) water channels provide a major pathway for osmotically driven water movement across epithelial and microvascular barriers in the lung. We used mice deficient in each of the three principal lung aquaporins, AQP1, AQP4 and AQP5, to test the hypothesis that aquaporins are important in neonatal lung fluid balance, adult lung fluid clearance and formation of lung oedema after acute lung injury. Wet-to-dry weight ratios (W/D) in lungs from wild-type mice decreased from 7.9 to 5.7 over the first hour after spontaneous delivery. AQP deletion did not significantly affect W/D at 45 min after birth. Alveolar fluid clearance was measured in living ventilated mice in which 0.5 ml saline containing radiolabelled albumin was instilled into the airspaces. Fluid clearance was 17.4 % in 15 min and inhibited >90 % by amiloride, but clearance was not affected by AQP deletion. W/D was measured in established models of acute lung injury - acid aspiration and thiourea administration. Two hours after intratracheal administration of HCl, W/D increased from 3.7 to 7.5 but was not affected by AQP deletion. Three hours after intraperitoneal infusion of thiourea, W/D increased to 5.5 and marked pleural effusions appeared, but there were no differences in wild-type and AQP knockout mice. Hyperoxic subacute lung injury was induced by 95 % oxygen. Neither mean survival (143 h) nor W/D at 65 h (5.1) were significantly affected by AQP deletion. Despite their role in osmotically driven lung water transport, aquaporins are not required for the physiological clearance of lung water in the neonatal or adult lung, or for the accumulation of extravascular lung water in the injured lung.

Topics: Acids; Age Factors; Animals; Animals, Newborn; Aquaporin 1; Aquaporin 4; Aquaporin 5; Aquaporins; Body Fluids; Hyperoxia; Indicators and Reagents; Membrane Proteins; Mice; Mice, Knockout; Pleural Effusion; Pulmonary Alveoli; Pulmonary Edema; Respiration, Artificial; Thiourea; Water-Electrolyte Balance

Reactive oxygen species (ROS) are involved in a number of disease states where they are believed to be responsible for cellular damage. In this study we examined the effect of ROS generation on polyamine catabolism. Treatment of human breast cancer cells with either H2O2 or hyperoxia increased the activity of spermidine/spermine N1-acetyltransferase (SSAT). These increases occurred before any significant signs of cellular injury. Agents known to decrease the production of reactive oxygen species such as dimethylthiourea and o-phenanthroline prevented the increase in SSAT activity indicating ROS involvement in the induction process. These results suggest that induction of SSAT may be a protective response to oxidative stress in mammalian cells facilitating removal of polyamines from the cell to prevent their toxic accumulation.

Topics: Acetyltransferases; Breast Neoplasms; Free Radical Scavengers; Free Radicals; Humans; Hyperoxia; Iron Chelating Agents; Phenanthrolines; Reactive Oxygen Species; Thiourea; Tumor Cells, Cultured