THE PERMSELECTIVITY OF GLOMERULAR-BASEMENT-MEMBRANE CAN BE COMPROMISED BY GLYCATION OR BY EXPOSURE TO LOW-LEVELS OF HYPOCHLORITE

Earlier studies indicated that chemically crosslinking glomerular base ment membrane (GEM) rendered it more permeable to water and to macromo lecules. Here possible mechanisms for the introduction of crosslinks i nto GEM under pathological conditions were explored. Glycation with gl ucose and with fructose over periods of 2 wk (fructose) and 6 weeks (g lucose) rendered the GEM more permeable to water and myoglobin as judg ed from in vitro ultrafiltration behaviour. The membranes were also ma de more permeable to serum following glycation. The permeation changes were shown to be dependent on glycoxidative reactions judging by thei r inhibition by EDTA and DTPA. Aminoguanidine also prevented glycation from altering the permeability of GEM. Fluorescence studies indicated the formation of bityrosine in glycated GEM. Studies with oxidants sh owed that while hydrogen peroxide superoxide and peroxynitrite had lit tle effect on GEM, hypochlorite anion was capable of increasing GEM pe rmeability to water, myoglobin, albumin and serum. Changes in permeati on were induced by very low quantities of hypochlorite, well within th e range of the amounts of hypochlorite formed by activated neutrophils . Thus glycoxidation, or oxidation by hypochlorite, are chemical mecha nisms by which GEM permeability can be increased. (C) 1997 Elsevier Sc ience B.V.