The lysosomal toxicity of aminoglycosides: a morphometric approach

Lysosomes of kidney proximal tubule cells have been described as an early target involved in aminoglycoside-induced nephrotoxicity. These organelles concentrate these molecules and are overloaded with osmiophilic lamellar material. Biochemical alterations of lysosomes have already been described. In this study 6 aminoglycosides were given i.p. at the doses of 10 and 50 mg/kg for 4-7-15 days. A morphometric study of the lysosomal system of rat kidney proximal tubules is described first using Delesse's principle on electron micrographics. After aminoglycoside treatment, lysosomal volume rose from 3.3% in controls up to 10% or more of the cell volume. Concomitantly lysosomes were overloaded with myeloid bodies up to 50% or more of their own volume. Individual measurements of lysosome sections were performed on micrographics: perimeter and area. Size distributions were compared to each other using the Kolmogorov-Smirnov statistical test. Since the observed distribution could not be compared with a normal, Poisson, or any other theoretical distribution, the size distribution of perimeters has been successfully likened to a sum of individual normal subpopulations, the means of which follow a geometrical progression of rate square root 2 from a constant value of 1.23 micron, with standard errors of 15% of their respective mean value. When converted to membrane area values the progression rate becomes 2 and suggests fusion of identical size lysosomes during their intracellular life.