AN ULTRASTRUCTURAL HISTOCHEMISTRY AND LIGHT-MICROSCOPY STUDY OF THE EARLY DEVELOPMENT OF RENAL PROXIMAL TUBULAR VACUOLATION AFTER A SINGLE ADMINISTRATION OF THE CONTRAST ENHANCEMENT MEDIUM IOTROLAN

The time course of contrast media (CM)-induced renal proximal tubular vacuolation was investigated in rats by light microscopy, transmission electron microscopy (TEM), and ultrastructural histochemistry for aci d phosphatase activity. Young adult male rats were created with a sing le dose of 3.0 g I/kg Iotrolan (Isovist(R) 300 mg I/ml) and sacrificed at 0 min, 5-min, 15-min, 2-hr, and 24-hr intervals, Light microscopy of vibratome sections of freshly excised tissue and of cryostat and pa raffin sections was also performed to allow comparison of the appearan ce of the vacuoles in the fresh state with light and electron microsco py, The sequence of events seen to occur can be summarized as follows. CM-induced vacuolation occurred at a low level as soon as 5 min after compound administration. The vacuolation was observed by TEM but coul d not be detected by light microscopy. This was followed by an increas e in size and I?umbers of vacuoles up to the 24-hr timepoint with a se quential increase in the staining for acid phosphatase activity of the vacuoles, most marked at the 24-hr timepoint. At timepoints less than 24 hr there appeared to be no marked increase in the normal complemen t of lysosomes or in the components of the Golgi-endoplasmic reticulum -lysosome pathway. At 24 hr, the vast majority, but not all, of the CM -induced vacuoles were positive for acid phosphatase activity. The int ensity of staining varied, and there was evidence of fusion of small l ysosomes with CM-induced vacuoles. These results suggest that formatio n of CM-induced vacuoles is a 2-stage process, following a normal path way for the handling of endogenous and exogenous substances.