A REVIEW OF DRUG-INDUCED LYSOSOMAL DISORDERS OF THE LIVER IN MAN AND LABORATORY-ANIMALS

Lysosomotropic agents are selectively taken up into lysosomes followin g their administration to man and animals [de Duve et al. (1974) Bioch em. Pharmacol. 23:2494-2531]. The effects of lysosomotropic drugs stud ied in vivo and in vitro can be used as models of lysosomal storage di seases. These agents include many drugs still used in clinical medicin e: aminoglycosides used in antibiotics [Tulkens (1988)]; phenothiazine derivatives; such antiparasitic drugs as chloroquine and suramin; ant iinflammatory drugs like gold sodium thiomalate; and cardiotonic drugs like sulmazol [Schneider (1992) Arch. Toxicol. 66:23-33]. Side-effect s to these drugs can be caused by their lysosomotropic properties. In addition to drugs, other compounds to which man and animals are expose d (e.g., metals, cytostatics, vitamins, hormones) are also lysosomotro pic. Liver cells, especially Kuppfer cells, are known to accumulate ly sosomotropic agents. Here we review studies which evaluate lysosomal c hanges in the liver following administration of lysosomotropic agents to experimental animals, and relate them to toxic side-effects or phar macological action, as was suggested by de Duve et al. (1974). Common features of lysosomal changes include, the overload of liver lysosomes by non-digestable material; increased size and number of liver lysoso mes; inhibition of several lysosomal enzymes; secondary increase in th e activity of some lysosomal enzymes; increased autophagy, and fusion disturbances. There was no significant change in endocytosis, except f or an increase in the Triton WR 1339 model. (C) 1997 Wiley-Liss, Inc.