Chemically induced accumulation of phospholipids in canine organ systems

Abstract

Cationic amphiphilic drugs (CAD) are structurally characterized by their hydrophobic ring structure and hydrophilic side chain. Studies have shown that over 30 CADs with various pharmacological activities have the ability to induce phospholipid-like inclusions in peripheral blood cells and in organs such as lung, liver and spleen. SK&F 105685 is a novel cationic amphiphilic compound with immunomodulatory activity. It induces immune suppressor cell activity in many species. The purpose of this study was to determine if this compound induces cytoplasmic phospholipid inclusions in dogs.Heparinized blood samples were collected from male and female dogs after 14 and 85 days of treatment. Buffy coats were prepared and fixed with 2.5% glutaraldehyde - 2.0% paraformaldehyde with 50 μM CaCl2 in 0.1 M cacodylate buffer, pH 7.2. The pellets were processed to epoxy resin. Tissues from all organs were collected at necropsy in buffered formalin following 30 or 90 days of treatment, and processed for histopathologic evaluation.