The suramin-treated rat as a model of mucopolysaccharidosis. Variation in the reversibility of biochemical and morphological changes among different organs.
We have examined the reversibility of the biochemical and pathological changes induced in the spleen, kidney and lung of the suramin-treated rat which we have previously proposed as a useful model of the human condition, mucopolysaccharidosis (MPS). Rats were injected with a single intravenous dose of suramin (250 mg/kg) and allowed to survive for periods of up to 6 months. The organs were examined for suramin content, pathological changes, biochemical storage of glycosaminoglycans (GAGs) and for the blockage of the relevant hydrolytic enzymes. The extent and rate of suramin accumulation and the retention of the drug varied considerably between organs with the greatest concentration of suramin (4,000 micrograms/g) occurring in the kidney 2 weeks after injection. Suramin persisted at gradually decreasing levels in all organs for the duration of the experiment, remaining at the highest level (1,150 micrograms/g) in the kidney. The concentration of GAGs peaked 10-18 days after administration of the drug, in all organs. Within 6 months the level had returned to normal in the liver, spleen and lung, but remained elevated in the kidney. The activities of beta-glucuronidase and acid phosphatase were decreased in all organs at diminishing levels throughout the experiment. There was a significant increase in the activity of arylsulphatase B, except in the kidney, where the predominant effect was a reduction of activity. Recovery from the morphological changes was evident in all organs except the lung within 6 months of suramin administration. The reversibility of the biochemical and pathological changes in the various tissues is discussed and compared with the earlier results described for the liver (Rees et al. 1986) and the implications of using suramin for the treatment of human trypanosomiasis, onchocerciasis and AIDS are considered.
D000818:Animals; D004195:Disease Models, Animal; D006025:Glycosaminoglycans / Q000032:analysis; D007668:Kidney / Q000032:analysis / Q000473:pathology* / Q000648:ultrastructure; D008168:Lung / Q000032:analysis / Q000473:pathology* / Q000648:ultrastructure; D008247:Lysosomes / Q000201:enzymology; D008297:Male; D008854:Microscopy, Electron; D009083:Mucopolysaccharidoses / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D011919:Rats, Inbred Strains; D013154:Spleen / Q000032:analysis / Q000473:pathology* / Q000648:ultrastructure; D013498:Suramin / Q000378:metabolism / Q000494:pharmacology*; D014018:Tissue Distribution
D006025:Glycosaminoglycans; D013498:Suramin