Protective effect of lipophilic antioxidants on phorbol-induced acute lunginjury in rats

Objective: To determine whether the lipophilic antioxidant U-74389G can ame liorate the acute lung injury induced by phorbol myristate acetate (PMA) in our isolated lung model in rats, and to compare its activity with the intr acellular enzymes superoxide dismutase (SOD) or catalase, Design: Randomized, controlled study. Setting: Animal-care facility procedure room. Subjects: Forty-two adult male Sprague-Dawley rats each weighing 250-350 g, Interventions: Typical acute lung injury was induced successfully by PMA du ring 60 mins of observation. PMA (2 mug/kg) elicited a significant increase in microvascular permeability (measured by using the capillary filtration coefficient K-fc), lung weight gain, the lung weight/body weight ratio, pul monary arterial pressure, and the protein concentration of the bronchoalveo lar lavage fluid. Measurements and Main Results: Pretreatment with 1 mg of U-74389G significa ntly attenuated the acute lung injury induced by PMA, all parameters having decreased significantly (p < .001), The protective effect of U-74389G was dose dependent, but SOD (6,000 U/kg) or catalase (50,000 U/kg) exhibited no protective effect. Conclusions: U-74389G significantly ameliorates acute lung injury induced b y PMA in rats.