Tyloxapol confers durable protection against hyperoxic lung injury in the rat

We tested the hypothesis that the nonlipid components of Exosurf, tyloxapol (TY) and cetyl alcohol (CA), protect against hyperoxic lung injury by indu ction of the animals' endogenous antioxidant defenses. Adult rats were intr atracheally instilled with escalating doses of TY and CA (n = 20) or TY alo ne (n = 32) and immediately exposed to 100% oxygen. Intratracheal instillat ion of TY alone or in combination with CA Protected against lethal hyperoxi c injury ill the rat in a dose-dependent fashion. To assess the effects of timing, rats were instilled with TY pins CA 24 hours before (n = 6) and 24 hours after (n = 6) exposure to 100% oxygen, with time to death determined. Rats mere also instilled with TY alone at 0 hour (n = 6), 48 hours (n = 3) , 96 hours (n = 3), and 186 hours (n = 4) prior to exposure to 100% oxygen. Lungs mere assayed for superoxide dismutase, glutathione peroxidase, and c atalase activities. Finally, the pharmacokinetics of TY ill the rat lung we re determined by instilling radiolabelled TY intratracheally. ITT has a Pro longed half-life in the rat lung, and protection against lethal hyperoxic i njury was achieved by a single intratracheal dose delivered up to 186 hours prior to injury. Antioxidant enzymes mere not induced in protected animals . We conclude that TY provides durable protection against hyperoxic lung in jury without induction of antioxidant enzymes. It is present in the lung fo r sufficient duration to invoke a direct mechanism of protection, possible as a radical scavenger. These findings raise the prospect of a therapeutic application for TY as prophylaxis in patients at risk for oxygen toxicity a nd adult respiratory distress syndrome.