The suramin-treated rat as a model of mucopolysaccharidosis: reversibility of biochemical and morphological changes in the liver.
Rats treated with the trypanocidal drug suramin, a potent inhibitor of several lysosomal enzymes, develop a storage disorder which mimics the features of mucopolysaccharidosis (Constantopoulos et al. 1983). In this paper we have examined the reversibility of the biochemical and pathological changes induced in the liver of the suramin-treated rat. 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 liver was examined for suramin content, pathological changes, biochemical storage of glycosaminoglycans (GAGs) and for the blockade of the relevant hydrolytic enzymes. GAG storage in the liver peaked at approximately 14 days after administration of suramin when there was a five-fold increase in the GAG content. Thereafter GAGs decreased in parallel with the fall of suramin concentrations so that within 6 months the content had returned to control levels. The activity of most of the enzymes tested had also returned to control levels within 6 months. The pathological changes which are evident in the liver 1-2 weeks after administration of the drug had diminished considerably within 6 months. These results indicate that significant reversibility of both the biochemical and pathological changes induced by suramin occurs and they support the suitability of the suramin treated rat as a model to assess the value of therapeutic treatments of mucopolysaccharidosis.
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D006025:Glycosaminoglycans / Q000378:metabolism; D006867:Hydrolases / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008247:Lysosomes / Q000201:enzymology; D008297:Male; D008854:Microscopy, Electron; D009083:Mucopolysaccharidoses / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D009929:Organ Size / Q000187:drug effects; D009928:Organ Specificity; D051381:Rats; D011919:Rats, Inbred Strains; D013498:Suramin / Q000633:toxicity*; D013997:Time Factors
D006025:Glycosaminoglycans; D013498:Suramin; D006867:Hydrolases