Chloroquine‐Induced Accumulation of Gangliosides and Phospholipids in Skeletal Muscles

Abstract

High doses of the lysosomotropic drug chloroquine result in lipid storage in many organs in animals. We used miniature pigs, type Göttingen, to study the lipid accumulation in skeletal muscle after chloroquine intoxication for more than 200 days. The lipids of the quadriceps muscle in intoxicated and in age-matched control pigs were characterized and determined. The lipid storage was larger in skeletal muscle than in any other organ of the intoxicated pigs. The concentration of phospholipids was increased threefold, acidic phospholipids relatively more than neutral ones. The lysosome-specific acidic phospholipid bis(monoacylglyceryl)phosphate content was almost 50-fold larger in the intoxicated pigs than in the controls. Cholesterol was increased slightly more than the phospholipids, but there was no particular accumulation of cholesteryl esters, which has been shown to occur in the liver. For the first time a storage of gangliosides, relatively more pronounced than of other lipids, was demonstrated in skeletal muscle in the drug-induced lipidosis. The concentration of total gangliosides was increased 10--15-fold, and the pattern of gangliosides showed some distinct changes resulting in at least a 100-fold increase in the concentration of ganglioside GM2 (II3NeuAc-GgOse4Cer).