Bleomycin-Induced Lung Injury in the Rat: Effects of the Platelet-Activating Factor (PAF) Receptor Antagonist BN 52021 and Platelet Depletion

Bleomycin is a highly effective antitumor agent, but pulmonary toxicity, characterized by an acute inflammatory reaction and associated pulmonary edema, limits clinical use of the drug.Platelets and platelet-activating factor (PAF), a membrane-derived phospholipid, have been implicated in the mechanisms that can mediate pulmonary microvascular injury.We sought to investigate the role ofPAF in bleomycin-induced lung injury in the rat, using the PAF receptor antagonist BN 52021; and the role of platelets though the use of an anti-platelet antibody.Lung injury was induced by intratracheal bleomycin (1. 5 mg) and assessed by measurements oflung wet weight and total pulmonary extravascular albumin space (TPEAS).Bleomycin caused a significant increase in both indices after 48 hr, compared with control animals (p < 0.05).A single dose of BN 52021 (20 mg/kg orally) significantly reduced the bleomycin-induced increase in lung weight, but not the rise in TPEAS (p > 0.05).Increasing the dose of BN 52021 (20 mg/kg/12 hr, orally) had no additional effect.Reducing circulating platelet numbers by approximately 75 % had no effect on either the increase in lung weight or TPEAS, observed 48 hr after bleomycin (p > 0.05).PAF may partially contribute to the acute infiamtory reaction seen after intratracheal bleomycin in rats.