Autoxidation products of both carbohydrates and lipids are increased in uremic plasma: Is there oxidative stress in uremia?

Toshio Miyata, Min Xin Fu, Kiyoshi Kurokawa, Charles Van Ypersele De Strihou, Suzanne R. Thorpe, John W. Baynes

Research output: Contribution to journalArticle

136 Citations (Scopus)

Abstract

Background. Advanced glycation end products (AGEs), formed by non- enzymatic glycation and oxidation (glycoxidation) reactions, have been implicated in the pathogenesis of several diseases, including normoglycemic uremia. AGE research in uremia has focused on the accumulation of carbohydrate-derived adducts generated by the Maillard reaction. Recent studies, however, have demonstrated that one AGE, the glycoxidation product carboxymethyllysine (CML), could be derived not only from carbohydrates but also from oxidation of polyunsaturated fatty acids in vitro, raising the possibility that both carbohydrate and lipid autoxidation might be increased in uremia. Methods. To address this hypothesis, we applied gas chromatography-mass spectrometry and high performance liquid chromatography to measure protein adducts formed in uremic plasma by reactions between carbonyl compounds and protein amino groups: pentosidine derived from carbohydrate-derived carbonyls, malondialdehyde (MDA)-lysine derived from lipid-derived carbonyls, and CML originating possibly from both sources. Results. All three adducts were elevated in uremic plasma. Plasma CML levels were mainly (>95%) albumin bound. Their levels were not correlated with fructoselysine levels and were similar in diabetic and non-diabetic patients on hemodialysis, indicating that their increase was not driven by glucose. Pentosidine and MDA-lysine were also increased in plasma to the same extent in diabetic and non-diabetic hemodialysis patients. Statistical analysis indicated that plasma levels of CML correlated weakly (F < 0.05) with those of pentosidine and MDA-lysine, but that pentosidine and MDA-lysine varied independently (P > 0.5). Conclusions. These data suggest that the increased levels of AGEs in blood, and probably in tissues, reported in uremia implicate a broad derangement in non-enzymatic biochemistry involving alterations in autoxidation of both carbohydrates and lipids.

Original languageEnglish
Pages (from-to)1290-1295
Number of pages6
JournalKidney international
Volume54
Issue number4
DOIs
Publication statusPublished - 1998 Jan 1
Externally publishedYes

Keywords

  • AGEs
  • Carboxymethyllysine
  • Glycoxidation
  • Lipoxidation
  • Malondialdehyde- lysine
  • Non-enzymatic biochemistry
  • Oxidative protein damage
  • Pentosidine

ASJC Scopus subject areas

  • Nephrology

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