Induction of lysosomal storage by suramin.
Isolated livers of rats injected with saline or with suramin (250 mg per kg body weight) 24h previously were perfused with a medium containing radioactively labeled formaldehyde-treated albumin. Suramin-loaded livers released breakdown products at a much lower rate than controls and contained about the double amount of undigested radioactive protein up to about 3 h after the start of the perfusion. These results show that inhibition of proteolysis by suramin as reported previously (Davies et al., 1971; Buys et al., 1973) is not caused by binding of the drug to the substrate in the bloodstream. Electron micrographs of liver sections of suramin-treated rats showed that lysosomes of sinusoidal cells resembled those seen in certain lysosomal storage diseases. The effect of suramin on lysosomal enzymes was studied in vitro. When used at a concentration corresponding to the putative concentration in lysosomes in vivo, the drug inhibited the lysosomal endopeptidases cathepsin Bl and D as well as acid phosphatase. Inhibition of acid phosphatase by suramin in vivo could also be demonstrated by histochemical methods. These results suggest that the observed storage phenomena may be mainly caused by inhibition of lysosomal enzymes.
D000418:Albumins / Q000378:metabolism; D000818:Animals; D002403:Cathepsins / Q000494:pharmacology; D005557:Formaldehyde / Q000494:pharmacology; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D013498:Suramin / Q000494:pharmacology*; D013997:Time Factors
D000418:Albumins; D005557:Formaldehyde; D013498:Suramin; D002403:Cathepsins