Organomegaly and histopathology in an animal model of mucopolysaccharidosis induced by suramin

Abstract

The trypanocidal drug suramin causes glycosaminoglycan and sphingolipid accumulation in the rat, thus simulating a mucopolysaccharidosis (Constantopoulos et al. 1980). In this paper we report on the extent and nature of the morphological changes that occur in the liver, kidneys, spleen, heart, lung and brain as a result of short or long term suramin administration. The first group of rats received a single intravenous injection of suramin (500 mg/kg) and was sacrificed 3-9 days after the injection. The second group received low doses of suramin (50-90 mg/kg) at 2-3 weekly intervals over 3 months. Samples of the above mentioned organs were processed for light and electronmicroscopy and the remainder of the tissue weighed and assayed for total protein, DNA and RNA content. In both groups of rats, suramin caused an abnormal enlargement of the spleen, kidney, lung and liver, splenomegaly being the most pronounced. The total protein, and DNA content did not alter in the treated rats, however, the RNA content of the spleen increased 100%, 9 days after injection and there was a small but consistent increase in RNA content of the liver, kidney and lung. Significant pathological changes were observed in these organs and also in the brain and heart. The changes were similar in many respects to the pathology seen in the lysosomal storage disorder, mucopolysaccharidosis and further support the proposition that the suramin treated rat might be a useful experimental animal model of the disease. Several mechanisms by which suramin might produce organomegaly in the rat are discussed.