title: Accumulation of free adduct glycation, oxidation, and nitration products follows acute loss of renal function.
abstract: Glycation, oxidation, and nitration of endogenous proteins occur spontaneously and these modifications are also present in foods. Increased levels of these chemical changes are associated with chronic renal failure; however, little is known about acute kidney failure. We measured these modifications of plasma protein and related free adducts in plasma following bilateral nephrectomy and bilateral ureteral obstruction. Advanced glycation end-product (AGE) residues of plasma protein were increased 3 h post-surgery, and thereafter slowly decreased in all groups, reflecting changes in plasma protein synthesis and transcapillary flow post-surgery. Ureteral ligation increased oxidation and nitration adduct residues. There were, however, marked increases in AGE, dityrosine, or 3-nitrotyrosine free adducts in both nephrectomized and ureter-ligated rats compared to rats that had undergone sham operations. There were lower modified adduct concentrations in the ureter-ligated compared to the nephrectomized rats, reflecting residual glomerular filtration and tubular removal. There was no increase in glycated, oxidized, and nitrated proteins. Glyoxal and methylglyoxal were also increased in both renal failure models. Our study shows that the acute loss of renal function and urinary excretion leads to the accumulation of AGE, oxidation, and nitration free adducts in the plasma.
authors.affiliation: Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, Coventry, UK.
authors.forename: N
authors.initials: N
authors.lastname: Rabbani
authors.forename: K
authors.initials: K
authors.lastname: Sebekova
authors.forename: K
authors.initials: K
authors.lastname: Sebekova
authors.forename: A
authors.initials: A
authors.lastname: Heidland
authors.forename: P J
authors.initials: PJ
authors.lastname: Thornalley
mesh_terms: D000818:Animals; D001835:Body Weight / Q000502:physiology; D004195:Disease Models, Animal; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006037:Glyoxal / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000503:physiopathology; D008026:Ligation; D008297:Male; D009392:Nephrectomy; D018384:Oxidative Stress / Q000502:physiology; D011765:Pyruvaldehyde / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D017127:Glycation End Products, Advanced; C002744:3-nitrotyrosine; D014443:Tyrosine; D006037:Glyoxal; D011765:Pyruvaldehyde; C007543:dityrosine