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

• Published in: Environmental health perspectives 1990-04, Vol.85, p.65-69
• Main Authors: Evans, Timothy W., McAnulty, Robin J., Rogers, Duncan F., Chung, K. Fan, Barnes, Peter J., Laurent, Geoffrey J.
• Format: Article
• Language: English
• Subjects: 560300 - Chemicals Metabolism & Toxicology; Administration, Inhalation; Administration, Oral; Adult respiratory distress syndrome; Albumins; Albumins - analysis; Animals; ANTI-INFECTIVE AGENTS; ANTIBIOTICS; ANTIMITOTIC DRUGS; ANTINEOPLASTIC DRUGS; ANTIPYRETICS; BIOLOGICAL EFFECTS; BIOLOGICAL MATERIALS; BLEOMYCIN; Bleomycin - administration & dosage; Bleomycin - toxicity; BLOOD; BLOOD CELLS; BLOOD COUNT; BLOOD PLATELETS; BODY; BODY FLUIDS; CENTRAL NERVOUS SYSTEM DEPRESSANTS; Diterpenes; Dosage; Dose-Response Relationship, Drug; DRUGS; EDEMA; ESTERS; Extracellular Space - drug effects; Ginkgolides; Human resources; INFLAMMATION; INHIBITION; Lactones; LIPIDS; Lung Diseases - blood; Lung Diseases - chemically induced; Lung Diseases - pathology; Lung injury; LUNGS; Male; MATERIALS; MEMBRANE PROTEINS; Neutrophils; Organ Size - drug effects; ORGANIC COMPOUNDS; ORGANIC PHOSPHORUS COMPOUNDS; ORGANS; PATHOLOGICAL CHANGES; PHOSPHOLIPIDS; Platelet Activating Factor - antagonists & inhibitors; Platelet Activating Factor - physiology; Platelet Count - drug effects; Platelets; PROTEINS; RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT; Rats; Rats, Inbred Lew; RECEPTORS; RESPIRATORY SYSTEM; Symposium on Chemicals and Lung Toxicity. To Study the Agent or the Disease. July 24-25, 1988. Cardiff, Wales; SYMPTOMS; TOXICITY; Vehicles
• ISSN: 0091-6765; 1552-9924
• DOI: 10.2307/3430666

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 of PAF 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 of lung 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 inflammatory reaction seen after intratracheal bleomycin in rats.