The permselectivity of glomerular basement membrane can be compromised by glycation or by exposure to low levels of hypochlorite

[摘要] Earlier studies indicated that chemically crosslinking glomerular basement membrane (GEM) rendered it more permeable to water and to macromolecules. Here possible mechanisms for the introduction of crosslinks into GEM under pathological conditions were explored. Glycation with glucose and with fructose over periods of 2 wk (fructose) and 6 weeks (glucose) rendered the GEM more permeable to water and myoglobin as judged from in vitro ultrafiltration behaviour. The membranes were also made more permeable to serum following glycation. The permeation changes were shown to be dependent on glycoxidative reactions judging by their 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 showed that while hydrogen peroxide superoxide and peroxynitrite had little effect on GEM, hypochlorite anion was capable of increasing GEM permeability to water, myoglobin, albumin and serum. Changes in permeation were induced by very low quantities of hypochlorite, well within the range of the amounts of hypochlorite formed by activated neutrophils. Thus glycoxidation, or oxidation by hypochlorite, are chemical mechanisms by which GEM permeability can be increased. (C) 1997 Elsevier Science B.V.

[发布日期] 1997-08-22

[关键词] nephritis;diabetes mellitus;glycation;oxidant damage;glomerular filtration;hypochlorite