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Chemically Induced Accumulation of Phospholipids in Canine Organ Systems. II. Induction by Amiodarone and Chloroquine

Published online by Cambridge University Press:  02 July 2020

Beverly E. Maleeff
Affiliation:
SmithKline Beecham Pharmaceuticals, Department of Toxicology-US, King of Prussia, PA
Jeffrey A. Handler
Affiliation:
SmithKline Beecham Pharmaceuticals, Department of Toxicology-US, King of Prussia, PA
Calvert S. Louden
Affiliation:
SmithKline Beecham Pharmaceuticals, Department of Toxicology-US, King of Prussia, PA
Timothy K. Hart
Affiliation:
SmithKline Beecham Pharmaceuticals, Department of Toxicology-US, King of Prussia, PA
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Extract

Cationic amphiphilic drugs (CAD) are structurally characterized by their hydrophobic ring structure and hydrophilic side chain. While there is little known about the effect of CAD in dogs, studies in animal models have shown that over 30 CAD with various pharmacological activities have the ability to induce phospholipid-like inclusions in peripheral blood cells and in organs such as lung, liver, eye and spleen. Two CAD used for treatment of human disease are amiodarone, prescribed for arrythmia, and chloroquine, an antimalarial. The purpose of this study was to determine if these compounds induce cytoplasmic phospholipid inclusions in peripheral blood mononuclear cells (PBMC), polymorphonuclear lymphocytes (PMN), alveloar macrophages, liver and retina in dogs.

Samples were collected from male beagle dogs after 6 weeks of oral dosing with amiodarone (75 mg/kg/day) or chloroquine (75 mg/kg/day). Buffy coats were prepared from peripheral blood and fixed with 3% glutaraldehyde in 0.1 M phosphate buffer, pH 7.2. Alveolar macrophages were recovered from bronchoalveolar lavage fluid by centrifugation and the pellets fixed with buffered 2.5% glutaraldehyde-2% formaldehyde.

Type
Pathology
Copyright
Copyright © Microscopy Society of America 1997

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References

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4. This work was supported by SmithKline Beecham Pharmaceuticals.Google Scholar