Lysosomal Phospholipids from Rat Liver after Treatment with Different Drugs

Abstract

Rats were treated with 5 different drugs p-ethoxyacetanilide (I), indomethacin (II) and nor-amidopyrine-methanesulfonate (III), O,O''-bis(diethylaminoethyl)hexestrol (IV) and chloroquine (V) for 3-4 wk. Liver cell fractions were isolated by discontinuous gradient centrifugation and the specific activity of acid phosphatase was determined in each. Lysosomal fractions contained widely varying amounts of this marker enzyme, indicating that the concentration of lysosomes within these fractions differed. The amount and patterns of phospholipids reflected this fact. Since bis(monoacylglycero)phosphate [(MAG)2P; synonym: lysobisphosphatidic acid] is a marker lipid for secondary lysosomes, significant quantities of this acidic phospholipid were found only in those lysosomal fractions which were also rich in acid phosphatase (EC 3.1.3.2) activity. Some 12% of the lysosomal phospholipids from animals receiving the hexestrol derivative (IV), and 19% of those from the chloroquine (V) experiment were present as (MAG)2P. The fatty acid compositions of this lysosomal phospholipid were not the same in all lysosome fractions. The more (MAG)2P present in the lysosomes, the more unsaturated are the fatty acids. After treatment with chloroquine, more than 90% of the fatty acids from (MAG)2P are unsaturated; C22:6 represents about 70% of the total.