The renal excretion and retention of macromolecules: The chemical structure effect.
Five derivatives of polyaspartamide were used as macromolecular models to study the effect of chemical structure of macromolecules on their renal excretion and retention. The parent polymer was formed solely by N(2-hydroxyethyl)aspartamide units (I) and in its derivatives about 20% of 2-hydroxyethyl groups were randomly replaced by either n-butyl- (II), 2(4-hydroxyphenyl)ethyl- (III, N- dimethylamino propyl- (IV) or the aspartamide unit was modified to free aspartic acid carboxyl (V). The rate of clearance from the serum, the deposition in the kidney tissue in comparison with the deposition in reticuloendothelial system organs-liver and spleen, as well as tissue and cellular localisation of deposits were studied on rabbits and mice taking advantage of fluorescence labelling. The clearance of macromolecular models from the serum compartment by the glomerular filtration is mainly molecular weight controlled, while the retention of macromolecules possessing the same molecular weight by the kidney tubular epithelium is strongly affected chemical modification. About thirty and hundred times higher retentions due to reabsorption in proximal tubule were found with macromolecular models II and III respectively.
D000818:Animals; D007275:Injections, Intravenous; D007668:Kidney / Q000378:metabolism / Q000502:physiology*; D007678:Kidney Glomerulus / Q000502:physiology; D007684:Kidney Tubules / Q000502:physiology; D008099:Liver / Q000378:metabolism; D046911:Macromolecular Substances; D008297:Male; D051379:Mice; D008856:Microscopy, Fluorescence; D008970:Molecular Weight; D010455:Peptides / Q000008:administration & dosage / Q000097:blood / Q000652:urine*; D011817:Rabbits; D013154:Spleen / Q000378:metabolism; D013329:Structure-Activity Relationship
D046911:Macromolecular Substances; D010455:Peptides; C044870:alpha, beta-poly((2-hydroxyethyl)aspartamide-co-(4-hydroxyphenethyl)aspartamide)