X-ray microanalysis and electron microscopy of platinum complex in the epithelium of proximal renal tubules of the cisplatin administered rabbits

Abstract

The initial phase of endocytosis of cisplatin, an anti-tumor platinum agent, into epithelial cells of the proximal renal tubules of rabbits was studied using an X-ray microanalyser at the electron microscopic level. After one to 11 intravenous injections of cisplatin (1 mg/kg/daily), each rabbit was sacrificed with overdose of pentobarbital and small pieces of renal cortex were fixed with 4% glutaraldehyde and 2% osmium tetroxide. After binding on the surface of brush border, dense substance was taken up in endocytic vacuoles that proceeded into the center of epithelial cells leaving empty or scanty vacuoles in apical area. Both platinum and iron were detected in such intracellular dense substance. This shows the transcellular pathways of platinum complex. On the other hand, intercellular pathways were not found in this experiment.