Advanced glycation and lipidoxidation of the peritoneal membrane: Respective roles of serum and peritoneal fluid reactive carbonyl compounds

被引:110
作者
Miyata, T [1 ]
Horie, K
Yeda, Y
Fujita, Y
Izuhara, Y
Hirano, H
Uchida, K
Saito, A
De Strihou, CV
Kurokawa, K
机构
[1] Tokai Univ, Sch Med, Inst Med Sci, Isehara, Kanagawa 2591193, Japan
[2] Tokai Univ, Sch Med, Dept Internal Med, Isehara, Kanagawa 2591193, Japan
[3] Iwafuji HOsp, Okayama, Japan
[4] Nagoya Univ, Sch Agr Sci, Nagoya, Aichi, Japan
[5] Catholic Univ Louvain, Serv Nephrol, B-1200 Brussels, Belgium
关键词
uremia; carbonyl stress; advanced glycation; lipoxidation; non-enzymatic biochemistry;
D O I
10.1046/j.1523-1755.2000.00182.x
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Background. Advanced glycation of proteins has been incriminated in the progressive alteration of the peritoneal membrane during chronic peritoneal dialysis (PD). Advanced glycation end products (AGEs) result from a modification of proteins by reactive carbonyl compounds (RCOs), RCOs resulting front glucose breakdown are present in commercial PD fluid. They also accumulate in uremic plasma. The present study was undertaken to evaluate the respective contribution of these two sources of RCOs in the genesis of peritoneal AGEs. Methods. Three major RCOs formed during heat sterilization of PD fluid, that is, glyoxal, methylglyoxal,and 3-deoxyglucosone, and total RCOs were measured in commercial PD fluid and in PD effluent. The generation of pentosidine, used as a surrogate marker for AGEs, during one-week incubations of PD fluid and effluent samples fortified with bovine serum albumin (BSA) was measured by high-performance liquid chromatography. Peritoneal samples were stained with antibodies specific for two AGEs derived from carbohydrate-dependent RCOs, N-l-(carboxymethyl)lysine (CML) and pentosidine, or for two advanced lipoxidation end products (ALEs) derived from lipid-dependent RCOs, malondialdehyde (MDA)-lysine and 4-hydroxynonenal (HNE)-protein adduct. Results. Glyoxal, methylglyoxal, and 3-deoxyglucosone were identified in commercial PD fluid. Their levels in FD effluents decreased with dwell time probably by diffusion into blood circulation. In contrast, the levels of total RCOs were initially low in commercial PD fluid, increased in PD effluent with dwell time probably by diffusion fl om circulation into the peritoneal cavity, and after 12 hours, reached values observed in uremic serum. The relevance of the rise in total RCOs fur AGE formation is demonstrated by a pat-allel increase in the generation of pentosidine during incubations of PD effluents. In contrast with RCOs present in glucose-rich PD fluid, RCOs diffusing from uremic circulation originate from both carbohydrates and lipids. Their role in the modification of peritoneal proteins is demonstrated by the immunohistochemical study of peritoneal tissue. Two AGEs and two ALEs increase in parallel in the mesothelial layers and in vascular wall of small arteries in the peritoneum. Conclusions. Protein modification of the peritoneum is determined not only by RCOs originating in PD fluid, but also by RCOs originating from the uremic circulation. The present data might be relevant to current attempts to improve PD fluid toxicity by lowering its glucose content.
引用
收藏
页码:425 / 435
页数:11
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