Studies on the nephrotoxicity of silicon

Until recently it was generally accepted that the main source of exposure to silicon in man was the occupational inhalation of silica dust. Contrary to previously held belief silicates have been shown to be absorbed from the alimentary tract and that the kidney is the main organ of excretion of dietary absorbed silicon. In man renal functional impairment is accompanied by a fall in urinary excretion of silicon and a rise in serum silicon (Bobbie et al 1981). For the past 50 years there have been several reports on the nephrotoxicity of a variety of silicon compounds administered to experimental animals by several different routes. Moreover, there have been claims that acute or chronic exposure to siliceous dusts or prolonged intake of drinking water with a high silica content resulted in renal lesions in man. Secure in the belief that silicon compounds were nonabsorbable and non-toxic there has been an increasing use of silicates by the food and pharmaceutical industries as anticaking, antifoaming or hygroscopic agents. Thus recent evidence that silicates are absorbed and that the kidney is the main route of excretion raises a natural concern for the liberal ingestion of silicates by man in in view of the reports of nephrotoxicity in the experimented animal. Whereas, the few previous investigations of silicon nephrotoxicity have been rather limited in nature and inconclusive as to the nature of the pathogenetic mechanism, this investigation has attempted a study in depth while bringing to bear on the problem many new and different investigative techniques. This investigation has examined the renal effects of intraperitoneal injection of four silicon compounds to which man may be exposed. The intraperitoneal route was chosen since it was found to be the most convenient and reliable method, whereby the kidney could be exposed to different levels, of serum silicon. A series of acute experiments in rats determined that high serum silicon levels resulted in a tubulo-interstitial lesion, which was most pronounced in and around the distal tubule and collecting ducts. Extensive electron microscopic examination of the lesions revealed that the damage was manifest in gross swelling and oedema of the epithelial cells and their cytoplasmic contents. A marked acute inflammatory response in which eosinophils were prominent accompanied the lesions. Significant glomerular pathology did not result from acute silicon nephrotoxicity. All four silicon compounds tested produced a similar degree of renal damage. Three different, but complementary techniques were then used to demonstrate the concentration and localisation of silicon in the kidney in the acute experimental model. Atomic absorption spectroscopic (A.A.S;) measurement of silicon in ashed samples showed an early and rapid rise in renal tissue silicon concentrations in contrast to a slower accumulation in other organs. The rarely studied radioactive isotope of silicon, 31Si which was specially made in an atomic reactor for this investigation, confirmed the A.A.S. findings while additionally providing autoradiographic studies which showed silicon concentration in the distal tubule. (Abstract shortened by ProQuest.)