Mild oxidative damage in the diabetic rat heart is attenuated by glyoxalase-1 overexpression

Olaf Brouwers, Joyce M.J. de vos-Houben, Petra M.G. Niessen, Toshio Miyata, Frans van Nieuwenhoven, Ben J.A. Janssen, Geja Hageman, Coen D.A. Stehouwer, Casper G. Schalkwijk

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)

Abstract

Diabetes significantly increases the risk of heart failure. The increase in advanced glycation endproducts (AGEs) and oxidative stress have been associated with diabetic cardiomyopathy. We recently demonstrated that there is a direct link between AGEs and oxidative stress. Therefore, the aim of the current study was to investigate if a reduction of AGEs by overexpression of the glycation precursor detoxifying enzyme glyoxalase-I (GLO-I) can prevent diabetes-induced oxidative damage, inflammation and fibrosis in the heart. Diabetes was induced in wild-type and GLO-I transgenic rats by streptozotocin. After 24-weeks of diabetes, cardiac function was monitored with ultrasound under isoflurane anesthesia. Blood was drawn and heart tissue was collected for further analysis. Analysis with UPLC-MSMS showed that the AGE Nε-(1-carboxymethyl)lysine and its precursor 3-deoxyglucosone were significantly elevated in the diabetic hearts. Markers of oxidative damage, inflammation, and fibrosis were mildly up-regulated in the heart of the diabetic rats and were attenuated by GLO-I overexpression. In this model of diabetes, these processes were not accompanied by significant changes in systolic heart function, i.e., stroke volume, fractional shortening and ejection fraction. This study shows that 24-weeks of diabetes in rats induce early signs of mild cardiac alterations as indicated by an increase of oxidative stress, inflammation and fibrosis which are mediated, at least partially, by glycation.

Original languageEnglish
Pages (from-to)15724-15739
Number of pages16
JournalInternational journal of molecular sciences
Volume14
Issue number8
DOIs
Publication statusPublished - 2013 Aug 12

Keywords

  • Cardiac function
  • Glycation
  • Glyoxalase-I
  • Oxidative stress
  • Oxo-aldehydes

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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