Drug-induced lysosomal storage of sulfated glycosaminoglycans in cultured bovine and human fibroblasts.
Several di-cationic amphiphilic compounds are known to cause lysosomal accumulation of sulfated glycosaminoglycans (sGAG) in intact rats and in cultured rat fibroblasts. The purpose of the present investigation was to examine whether this drug side effect also occurs in bovine and human cells. Cultured fibroblasts from both species were exposed to tilorone (3 microM and 5 microM) for 72 h; lysosomal sGAG-storage was demonstrated by cytochemical staining with cuprolinic blue and by measuring the intracellular accumulation of [35S]-GAG. The cytological alterations as well as the radiochemical results in both species were in good agreement with previous data from rat fibroblasts. The present findings indicate that the drug-induced lysosomal storage of sGAG is a species-independent phenomenon. Thus, cultured bovine and human fibroblasts are a suitable model for further studies concerning the as yet unknown molecular mechanisms underlying this adverse drug action.
Lüllmann-Rauch
R
R
Department of Anatomy, University of Kiel, Federal Republic of Germany.
Ziegenhagen
M
M
D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D005347:Fibroblasts / Q000648:ultrastructure*; D006025:Glycosaminoglycans / Q000378:metabolism*; D006651:Histocytochemistry; D006801:Humans; D007211:Indoles; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008854:Microscopy, Electron; D009942:Organometallic Compounds; D013194:Staining and Labeling; D013431:Sulfates / Q000378:metabolism; D013994:Tilorone / Q000494:pharmacology*
D006025:Glycosaminoglycans; D007211:Indoles; D009942:Organometallic Compounds; D013431:Sulfates; C015445:copper phthalocyanine; D013994:Tilorone