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Int. J. Mol. Sci. 2013, 14(8), 15724-15739; doi:10.3390/ijms140815724

Mild Oxidative Damage in the Diabetic Rat Heart Is Attenuated by Glyoxalase-1 Overexpression

Laboratory for Metabolism and Vascular Medicine, Division of General Internal Medicine, Department of Internal Medicine, Maastricht University Medical Center, Universiteitssingel 50, PO Box 616 (#14), 6200MD Maastricht, The Netherlands
Department of Toxicology, Maastricht University Medical Center, 6200MD Maastricht, The Netherlands
Centre of Translational and Advanced Research, Tohoku University, Sendai 980-8575, Japan
Department of Physiology, Maastricht University Medical Center, 6200MD Maastricht, The Netherlands
Department of Pharmacology, Maastricht University Medical Center, 6200MD Maastricht, The Netherlands
Author to whom correspondence should be addressed.
Received: 27 May 2013 / Revised: 26 June 2013 / Accepted: 8 July 2013 / Published: 29 July 2013
(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease)
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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. View Full-Text
Keywords: glycation; oxo-aldehydes; glyoxalase-I; oxidative stress; cardiac function glycation; oxo-aldehydes; glyoxalase-I; oxidative stress; cardiac function

This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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MDPI and ACS Style

Brouwers, O.; Vos-Houben, J.M.J.; Niessen, P.M.G.; Miyata, T.; Nieuwenhoven, F.V.; Janssen, B.J.A.; Hageman, G.; Stehouwer, C.D.A.; Schalkwijk, C.G. Mild Oxidative Damage in the Diabetic Rat Heart Is Attenuated by Glyoxalase-1 Overexpression. Int. J. Mol. Sci. 2013, 14, 15724-15739.

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