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

1,* email, 2email, 1email, 3email, 4email, 5email, 2email, 1email and 1email
Received: 27 May 2013; in revised form: 26 June 2013 / Accepted: 8 July 2013 / Published: 29 July 2013
(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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.
Keywords: glycation; oxo-aldehydes; glyoxalase-I; oxidative stress; cardiac function
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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.

AMA Style

Brouwers O, Vos-Houben JMJ, Niessen PMG, Miyata T, Nieuwenhoven FV, Janssen BJA, Hageman G, Stehouwer CDA, Schalkwijk CG. Mild Oxidative Damage in the Diabetic Rat Heart Is Attenuated by Glyoxalase-1 Overexpression. International Journal of Molecular Sciences. 2013; 14(8):15724-15739.

Chicago/Turabian Style

Brouwers, Olaf; Vos-Houben, Joyce M.J.; Niessen, Petra M.G.; Miyata, Toshio; Nieuwenhoven, Frans V.; Janssen, Ben J.A.; Hageman, Geja; Stehouwer, Coen D.A.; Schalkwijk, Casper G. 2013. "Mild Oxidative Damage in the Diabetic Rat Heart Is Attenuated by Glyoxalase-1 Overexpression." Int. J. Mol. Sci. 14, no. 8: 15724-15739.

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