Effects of suramin, a polyanionic drug inducing lysosomal storage disorders on tooth germs in vitro

Abstract

Suramin, a potent inhibitor of lysosomal enzymes, is commonly employed as a tool for inducing experimental mucopolysaccharidosis and lipidosis. The effects of the drug on embryonic mouse molars were analysed. Presecretory ameloblasts and odontoblasts were loaded with lysosome-like vacuoles. Staining with MC22-33F, an antibody to choline phospholipids and sphingomyelin, was completely reversed in the suramin-treated germs, in that it stained only presecretory ameloblasts (versus odontoblasts and some pulpal cells in the control group), according to a developmentally regulated pattern. The suramin-induced cytoplasmic changes were reminiscent of the features of mucopolysaccharidoses and lipidoses. The basement membrane, separating the enamel organ from the dental papilla, displayed suramin-induced patches, and in predentin collagen fibrillogenesis was found to be disturbed. Furthermore, autoradiography was employed to reveal uptake and distribution of [3H] suramin in the cells and predentin. Finally, a suramin-induced disturbance of the metabolism of sulphated macromolecules was found. The results imply that suramin effects in vitro on tooth germs can be used as a useful experimental model with to study both the action of the drug as well as cell and extracellular matrix perturbations in a mucopolysaccharidosis-like condition.

Suramin induces and enhances apoptosis in a model of hyperoxia-induced oligodendrocyte injury

“…Interference with growth factor receptor function (Gorospe et al, 1996), induction of lysosomal storage defects (Gritli-Linde et al, 1994), inhibition of enzymes involved in cell growth and proliferation such as protein kinase C may contribute to the cytostatic activity of the compound. Its efficacy as a chemotherapeutic agent has been shown for different types of cancer such as prostate cancer.…”