Plasma clearance, tissue distribution and catabolism of cationized albumins with increasing isoelectric points in the...

The infusion of cationic substances produces acute renal failure and proteinuria, and an experimental disease very similar to disseminated coagulopathy. The purpose of this work was to investigate further, in the rat, the plasma disappearance rate, the tissue distribution and the catabolism of albumins with modified isoelectric points. Human serum albumin was cationized with hexanediamine and labelled with 125I or 131I. During 10-180 min after their intravenous injection into the rat, these modified 125I-labelled albumins were cleared from the plasma at a rate which increased with their isoelectric point. At 1 and 3 h after the injection of highly cationic proteins (isoelectric point higher than 9.5) the tissue protein bound 125I concentration was greatest (approximately 3.5% of the injected activity/g) in the spleen and liver. A significant amount of the basic proteins was found in the kidney and in the lung (0.75-1%/g). Their concentration was much lower in other tissues. The whole body radioactivity was significantly lower 24 h after the injection of 131I-labelled cationized albumins than after similarly labelled native albumin. However, expressed as a percentage of the retention at 24 h, the body radioactivity at later times was higher for cationic than for native albumin. We conclude that cationized albumins are cleared from the plasma, mainly by the reticuloendothelial system, at a rate directly related to their isoelectric point. The cationized albumins are catabolized very rapidly initially, but a fraction of the injected protein remains in the body for a longer time than native albumin.