Polymorphonuclear leukocyte injury by methylglyoxal and hydrogen peroxide: A possible pathological role for enhanced oxidative stress in chronic kidney disease

Masaaki Nakayama, Keisuke Nakayama, Wan Jun Zhu, Yuko Shirota, Hiroyuki Terawaki, Toshinobu Sato, Masahiro Kohno, Sadayoshi Ito

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

Background. Accelerated burst of polymorphonuclear leukocytes (PMNs) may be involved in the primary pathology of enhanced oxidative stress in patients with chronic kidney disease (CKD); however, the precise mechanism remains unknown. Methylglyoxal (MGO), an α-oxoaldehyde reportedly elevated in CKD, could induce apoptosis in several cell lines, and generates radicals by the reaction with hydrogen peroxide (H2O2). Thus, we tested if a high MGO of uraemic milieu could play a role in PMN injury by interaction with H 2O2. Method. Cellular viability of PMNs, isolated from healthy volunteers, was tested by ATP chemiluminescence levels under MGO and/or H2O2, or 4-β phorbol 12-β-myristate 13-α-acetate (PMA). Superoxide anion (O2-) generation and apoptosis were measured by the reduction of ferricytochrome C and fluorocytometric analysis, respectively. Plasma MGO levels were measured by mass spectometry in 29 CKD patients. Results. At low levels of MGO (1-10 μM) and H2O2 (12.5 μM), no differences were found in cellular viability as compared to controls, whereas their combination significantly decreased PMN viability. PMA stimulation enhanced cellular injury of MGO by a function of MGO levels and preincubation with 5,5-dimethyl-1- pyrroline-N-oxide (free radical trap agent) attenuated it. MGO suppressed O 2- generation by PMA, while it accelerated apoptotic ratios in PMNs. Significant increases of plasma MGO and C-reactive protein levels were found by a function of CKD stage, and clinical level of MGO could induce PMN injury in combination with H2O2. Conclusion. These results indicate the combinatory effect of MGO and H2O 2 on PMN oxidative injury, and this pathology may be linked to enhanced oxidative stress in CKD.

Original languageEnglish
Pages (from-to)3096-3102
Number of pages7
JournalNephrology Dialysis Transplantation
Volume23
Issue number10
DOIs
Publication statusPublished - 2008 Oct

Keywords

  • Chronic kidney disease
  • Hydrogen peroxide
  • Methylglyoxal
  • Oxidative stress
  • Polymorphonuclear leukocyte

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

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