A FREE-RADICAL SCAVENGER (LAZAROID U75412E) ATTENUATES TUMOR-NECROSIS-FACTOR-ALPHA GENERATION IN A RABBIT MODEL OF SMOKE-INDUCED LUNG INJURY

The lazaroid (21-aminosteroid) analogue U75412E was evaluated in rabbi ts exposed to diesel fuel-polycarbonate plastic smoke. Inhalation of a total of 4.6 mg U75412E aerosolized at a rate of 1.53 mg/min for 3 mi n before or after smoke significantly prevented or limited the extent of alveolar hypoventilation, interstitial edema, and tumor necrosis fa ctor-alpha (TNF-alpha) by pulmonary alveolar macrophages (PAM) ex vivo observed at 2 h. The smoke-induced changes in wet lung/body weight ra tios and the production of superoxide (O-2(-)) by PAM ex vivo were als o attenuated by the drug treatment after smoke exposure (p < 0.05). Th is study suggests that lazaroids may ameliorate the oxygen-radical-ini tialed cytokine processes and inflammation cascade as a result of the smoke insult.