Mucopolysaccharidosis-like alterations in cardiac valves of rats treated with tilorone.
The purpose of this study was to examine whether the aortic and mitral valves of rats are involved in the mucopolysaccharidosis-like disorder induced by tilorone. Rats were treated with large doses of the drug for periods of 1-21 weeks. After chronic drug treatment the leaflets of both heart valves were thickened and opaque. In all treated animals the spongiosa layer of the stroma was crowded with vacuolated cells; the fibrosa layer was altered only after prolonged treatment. Ultrastructurally, the vacuolated cells of the spongiosa could be identified as histiocytes and fibroblasts, the former being the most susceptible cell type. The fibroblasts of the fibrosa represented the least sensitive cell type. The histochemical results showed that the clear cytoplasmic vacuoles in the spongiosa cells were due to lysosomal storage of polyanionic material with staining characteristics similar to cartilage matrix. After discontinuation of drug treatment the alterations persisted for several weeks. The present study shows that heart valves are involved in the mucopolysaccharidosis-like disorder induced by tilorone. The molecular pathomechanism of the disorder and the exact identification of the storage material must await further analysis.
Horstmann
G
G
Lüllmann-Rauch
R
R
D000818:Animals; D001021:Aortic Valve / Q000473:pathology*; D004705:Endocytosis; D005260:Female; D005347:Fibroblasts / Q000648:ultrastructure; D005449:Fluorenes / Q000633:toxicity*; D006644:Histiocytes / Q000648:ultrastructure; D008247:Lysosomes / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D008943:Mitral Valve / Q000473:pathology*; D009083:Mucopolysaccharidoses / Q000139:chemically induced* / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D013194:Staining and Labeling; D013994:Tilorone / Q000633:toxicity*; D013997:Time Factors; D014617:Vacuoles / Q000648:ultrastructure
D005449:Fluorenes; D013994:Tilorone