Mercury accumulation in kidney lysosomes of proteinuric rats

Abstract

The purpose of the present study was to determine whether lysosomal accumulation of mercury in the kidney is due to a leakage of protein-bound mercury through the glomerular filtration barrier followed by reabsorption into the lysosomal system of the proximal tubule. The subcellular distribution of mercury in the kidney was studied in four different groups of rats with and without proteinuria: normal young rats, young rats with aminonucleoside nephrosis, old rats with spontaneous proteinuria, and old rats with chronic mercury intoxication and proteinuria. Radioactive mercuric chloride (203HgCl2) was injected s.c. into the rats 72 hours before sacrifice. Cell fractionation experiments were carried out on homogenates of the renal cortex by differential centrifugation. Determination of radioactive mercury in the subcellular fractions revealed that mercury was concentrated in the lysosomal fraction of all rats with proteinuria. In contrast, normal rats without proteinuria had the highest concentration of mercury in the supernatant, and there was no enrichment of mercury in the lysosomal fraction. Gel filtration chromatography performed on urine samples from proteinuric rats demonstrated that excreted mercury was associated with the albumin fraction. The accumulation of mercury in renal lysosomes of proteinuric rats and the demonstration of mercury bound to albumin in the urine support the hypothesis that mercury bound to plasma proteins passes the glomerular filtration barrier in proteinuric conditions and enters the lysosomal system of the proximal tubule by way of endocytosis.