Assessment of oxidative stress in lungs from sheep after inhalation of wood smoke

To elucidate potential dose-dependent mechanisms associated with wood smoke inhalation injury, the present study evaluated antioxidant status and the extent of pulmonary injury in sheep after graded exposure to smoke. Adult, male sheep (n=4-5 per group) were anesthetized and received 0, 5, 10 or 16 units of cooled western pine bark smoke, corresponding to 0, 175, 350 and 560s, respectively, of smoke dwell time in the airways and lung. Smoke was mixed at a 1:1 ratio with 100% O₂ to minimize hypoxia. Plasma and expired breath samples were collected pre-smoke, and 6, 12, 18, 24, 36 and 48h after smoke exposure. Sheep were euthanatized 48h after smoke exposure and lung and airway sections were evaluated histologically for injury and biochemically for indices of oxidative stress. Plasma thiobarbituric acid reactive substances (TBARS) were 66 and 69% higher than controls after moderate and severe smoke exposure at 48h, whereas total antioxidant potential was not statistically different among groups at any time after exposure. Lung TBARS showed a dose-dependent response to smoke inhalation and were approximately 2-, 3- and 4-fold higher, respectively, than controls after exposure to 5, 10 and 16units of smoke. Lung myeloperoxidase (MPO) activity was also higher in smoke-exposed animals than controls, and MPO activity was markedly elevated (19- and 22-fold higher than controls in right apical and medial lobes) in response to severe smoke exposure. Smoke exposure also induced a dose-dependent injury to tracheobronchial epithelium and lung parenchyma. Taken together these data show that few indices of oxidative stress responded in a dose-dependent manner to graded doses of smoke inhalation, although most of the indices measured in lung were affected by the highest dose of smoke. Additional time course studies are necessary to determine whether these oxidants are a cause or a consequence of the airway and lung injury associated with exposure to wood smoke.